bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes duplicated by polyploidy show unequal contributions to the transcriptome and organ-specific reciprocal silencing
Authors: Adams Keith L. , Cronn Richard , Percifield Ryan , Wendel Jonathan F.
Published: April 2003

Most eukaryotes have genomes that exhibit high levels of gene redundancy, much of which seems to have arisen from one or more cycles of genome doubling. Polyploidy has been particularly prominent during flowering plant evolution, yielding duplicated genes (homoeologs) whose expression may be retained or lost either as an immediate consequence of polyploidization or on an evolutionary timescale. Expression of 40 homoeologous gene pairs was assayed by cDNA-single-stranded conformation polymorphism in natural (1- to 2-million-yr-old) and synthetic tetraploid cotton (
Gossypium
) to determine whether homoeologous gene pairs are expressed at equal levels after polyploid formation. Silencing or unequal expression of one homoeolog was documented for 10 of 40 genes examined in ovules of
Gossypium hirsutum.
Assays of homoeolog expression in 10 organs revealed variable expression levels and silencing, depending on the gene and organ examined. Remarkably, silencing and biased expression of some gene pairs are reciprocal and developmentally regulated, with one homoeolog showing silencing in some organs and the other being silenced in other organs, suggesting rapid subfunctionalization. Duplicate gene expression was examined in additional natural polyploids to characterize the pace at which expression alteration evolves. Analysis of a synthetic tetraploid revealed homoeolog expression and silencing patterns that sometimes mirrored those of the natural tetraploid. Both long-term and immediate responses to polyploidization were implicated. Data suggest that some silencing events are epigenetically induced during the allopolyploidization process.
Protein trans-splicing in transgenic plant chloroplast: Reconstruction of herbicide resistance from split genes
Authors: Chin Hang Gyeong , Kim Gun-Do , Marin Ivan , Mersha Fana , Evans Thomas C. , Chen Lixin , Xu Ming-Qun , Pradhan Sriharsa
Published: April 2003

Inteins are intervening protein sequences that undergo self-excision from a precursor protein with concomitant joining of the flanking sequences. Here, we demonstrate intein trans-splicing in
Nicotiana tabacum
chloroplasts by using the naturally split
Ssp
DnaE intein. Trans-splicing occurred whether both intein fragments were encoded in the chloroplast or were separated into the chloroplast and nuclear genomes. A biolistic approach was used to integrate two fusion genes, one encoding aminoglycoside-3-adenyltransferase (
aadA
) and the first 123 aa of the
Ssp
DnaE intein (In) and the other encoding 36 C-terminal amino acid residues of the
Ssp
DnaE intein (Ic) and soluble modified green fluorescent protein (
smGFP
) into
N. tabacum
plastids. Expression of these gene fragments in the chloroplast resulted in ligated aadA-smGFP due to In-Ic-mediated trans-splicing. Furthermore, an N-terminal portion of the herbicide resistance gene
5-
enol
pyruvylshikimate-3-phosphate synthase
(
EPSPS
) containing a chloroplast localization signal fused to
In
(
EPSPSn-In
) was integrated into the nuclear DNA of
N. tabacum
by using
Agrobacterium tumefaciens
-mediated transformation. The remaining
EPSPS
gene fragment (
EPSPSc
) fused to
Ic
(
Ic-EPSPSc
) was integrated into the chloroplast genome by homologous recombination. Western blot analysis of cell extracts from these plants showed a full-length EPSPS, demonstrating that the
EPSPSn-In
gene product migrated to the chloroplast and underwent trans-splicing. Furthermore, these transgenic plants displayed improved resistance to the herbicide
N
-(phosphonomethyl)glycine (glyphosate) when compared with wild-type
N. tabacum
.
Engineering the proteolytic specificity of activated protein C improves its pharmacological properties
Authors: Berg David T. , Gerlitz Bruce , Shang Jing , Smith Tommy , Santa Paula , Richardson Mark A. , Kurz Ken D. , Grinnell Brian W. , Mace Ken , Jones Bryan E.
Published: April 2003

Human activated protein C (APC) is an antithrombotic, antiinflammatory serine protease that plays a central role in vascular homeostasis, and activated recombinant protein C, drotrecogin alfa (activated), has been shown to reduce mortality in patients with severe sepsis. Similar to other serine proteases, functional APC levels are regulated by the serine protease inhibitor family of proteins including α
1
-antitrypsin and protein C inhibitor. Using APC–substrate modeling, we designed and produced a number of derivatives with the goal of altering the proteolytic specificity of APC such that the variants exhibited resistance to inactivation by protein C inhibitor and α
1
-antitrypsin yet maintained their primary anticoagulant activity. Substitutions at Leu-194 were of particular interest, because they exhibited 4- to 6-fold reductions in the rate of inactivation in human plasma and substantially increased pharmacokinetic profiles compared with wild-type APC. This was achieved with minimal impairment of the anticoagulant/antithrombotic activity of APC. These data demonstrate the ability to selectively modulate substrate specificity and subsequently affect
in vivo
performance and suggest therapeutic opportunities for the use of protein C derivatives in disease states with elevated serine protease inhibitor levels.
Retention of NMDA receptor NR2 subunits in the lumen of endoplasmic reticulum in targeted NR1 knockout mice
Authors: Fukaya Masahiro , Kato Akira , Lovett Chanel , Tonegawa Susumu , Watanabe Masahiko
Published: April 2003

Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system, and the
N
-methyl-
d
-aspartate-selective glutamate receptor (NR) consisting of the NR1 subunit and an NR2 or NR3 subunit plays crucial roles in synaptic transmission, plasticity, and learning and memory. By using a knockout mouse strain, in which the NR1 gene deletion is primarily targeted to the CA1 pyramidal cells of the hippocampus, we investigated the
in vivo
effect of the loss of the NR1 subunit on the cellular expression and intracellular distribution of the NR2 subunits. The NR1 gene deletion had no apparent effect on the levels of NR2A or NR2B mRNA but led to severe reductions of NR2A and NR2B protein in dendrites of CA1 pyramidal cells. This reduced dendritic distribution of the NR2 subunits accompanied their robust accumulation in perikarya, where they were condensed in the lumen of the endoplasmic reticulum as electron-dense granules. These granules were also observed in CA1 pyramidal cells of the control mice but they were much fewer and contained no detectable levels of the NR2 subunit. The effect of the NR1 knockout on intracellular localization of the NR2 subunits was specific in that no such effect was observed for the GluR1 and PSD-95, two other major postsynaptic proteins. These results suggest that the NR1 subunit plays a crucial role in the release of the NR2 subunit from the endoplasmic reticulum in hippocampal pyramidal cells
in vivo
, and when the NR1 subunit is unavailable, the NR2 subunits are retained and aggregate into intracisternal granules.
Identification of Down's syndrome critical locus gene
SIM2-s
as a drug therapy target for solid tumors
Authors: DeYoung Maurice Phil , Tress Matthew , Narayanan Ramaswamy
Published: April 2003

We report here a cancer drug therapy use of a gene involved in Down's syndrome. Using bioinformatics approaches, we recently predicted
Single Minded 2
gene (
SIM2
) from Down's syndrome critical region to be specific to certain solid tumors. Involvement of
SIM2
in solid tumors has not previously been reported. Intrigued by a possible association between a Down's syndrome gene and solid tumors, we monitored
SIM2
expression in solid tumors. Isoform-specific expression of
SIM2
short-form (
SIM2-s
) was seen selectively in colon, prostate, and pancreatic carcinomas but not in breast, lung, or ovarian carcinomas nor in most normal tissues. In colon tumors,
SIM2-s
expression was seen in early stages. Antisense inhibition of
SIM2-s
expression in a colon cancer cell line caused inhibition of gene expression, growth inhibition, and apoptosis. The administration of the antisense, but not the control, oligonucleotides caused a pronounced inhibition of tumor growth in nude mice with no major toxicity. Our findings provide a strong rationale for the genes-to-drugs paradigm, establish
SIM2-s
as a molecular target for cancer therapeutics, and may further understanding of the cancer risk of Down's syndrome patients.
3β-Acetoxyandrost-1,5-diene-17-ethylene ketal functions as a potent antiandrogen with marginal agonist activity
Authors: Miyamoto Hiroshi , Marwah Padma , Marwah Ashok , Lardy Henry , Chang Chawnshang
Published: April 2003

The majority of available antiandrogens have been reported to possess agonist activity to induce prostate-specific antigen, which might result in antiandrogen withdrawal syndrome. Here we report the identification of 3β-acetoxyandrost-1,5-diene-17-ethylene ketal (ADEK) from dehydroepiandrosterone metabolites and derivatives as a potent antiandrogen. We found ADEK could interrupt androgen binding to the androgen receptor (AR) and suppress androgen-induced transactivations of WT AR and a mutant AR in prostate cancer cells. ADEK inhibited prostate-specific antigen expression as well as growth in LNCaP prostate cancer cells stimulated by androgen. Importantly, ADEK had only marginal agonist effects, as compared with commonly used antiandrogens such as hydroxyflutamide and bicalutamide, leading to a lower possibility of inducing withdrawal response. Moreover, ADEK could block an adrenal androgen androstenediol-induced AR transactivation that hydroxyflutamide and bicalutamide failed to block. These unique antiandrogenic activities make ADEK a potential therapeutic compound that might be able to inhibit AR-mediated prostate cancer progression. Further
in vivo
studies might facilitate the development of a better antiandrogen for the treatment of prostate cancer.
Endothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice
Authors: Jones Steven P. , Greer James J. M. , van Haperen Rien , Duncker Dirk J. , de Crom Rini , Lefer David J.
Published: April 2003

Congestive heart failure results in cardiovascular dysfunction and diminished vascular nitric oxide (NO) production. We hypothesized that overexpression of endothelial NO synthase (eNOS) within the endothelium would reduce the extent of contractile dysfunction in a murine model of infarct-induced congestive heart failure. We generated transgenic (TG) mice overexpressing the human eNOS gene. The TG mice displayed significantly enhanced eNOS protein levels and eNOS activity levels (10- to 12-fold greater) in the aorta and the coronary vasculature. Non-TG (NTg) and eNOS TG mice were subjected to permanent left anterior descending coronary artery occlusion and then observed for 1 mo. We assessed cardiac function
in vivo
by using echocardiography and ultraminiature ventricular pressure catheters. Myocardial infarct size was similar between study groups (≈70% of the risk zone). Survival was increased by 43% in the eNOS TG mice compared with NTg (
P
< 0.05). Fractional shortening and cardiac output were also significantly (
P
< 0.05) greater in the eNOS TG than in NTg. Interestingly, pulmonary edema was evident only in NTg mice, and no evidence of pulmonary edema was observed in the eNOS TG mice. Thus, targeted overexpression of the eNOS gene within the vascular endothelium in mice attenuates both cardiac and pulmonary dysfunction and dramatically improves survival during severe congestive heart failure.
A simulation method and distributed server balancing results of networked industrial robots for automotive welding and assembly lines
Authors: Ranky Paul G.
Published: April 2003

The fundamental purpose of building simulation models is because it is often impossible to experiment with real‐world systems. In terms of our networked robots in the automotive welding and assembly lines, simulating possible scenarios, both for design as well as for operation control purposes, is very important for the design team, as well as for management, due to the per‐minute‐cost of every failed robotic operation. In order to support, both the design as well as the management community of such systems, in this article, we discuss a generic simulation methodology, using the IT‐Guru OPNET simulation program, as well as show practical results, that demonstrate the benefits of simulation methods.
Customer satisfaction measurement in a business‐to‐business context: a conceptual framework
Authors: Rossomme Jeanne
Published: April 2003

In practice, firms measure customer satisfaction using models and theory developed for evaluating the perceptions of individual consumers rather than entire organizations. This paper develops an integrated model of customer satisfaction measurement specific to a business‐to‐business context and addresses the unique challenges inherent in this context by incorporating learnings from the fields of customer satisfaction, organizational buying behavior and relationship marketing. After presenting the model and its rationale, the paper illustrates practical uses of the model as a managerial tool for framing a system of customer satisfaction measurement.
Supply chain complexity and delivery performance: an international exploratory study
Authors: Milgate Michael
Published: April 2003

As just‐in‐time delivery has become increasingly commonplace and customer demands continue to tighten, the importance of fast, reliable delivery performance cannot be overstated. This is particularly true for organisations competing internationally, where the complexity of the supply chain must be managed within a global network. A conceptual model is presented that identifies three basic dimensions of this complexity. Results support the linkage of uncertainty with performance, however, no evidence was found that increased technological intricacy or more complicated organisational systems hamper delivery performance. Managers appear to have adopted mechanisms to accommodate these last two dimensions of complexity.
OCTONIONIC REALIZATIONS OF ONE-DIMENSIONAL EXTENDED SUPERSYMMETRIES: A CLASSIFICATION
Authors: CARRION H. L. , ROJAS M. , TOPPAN F.
Published: April 2003

The classification of the octonionic realizations of the one-dimensional extended supersymmetries is here furnished. These are non-associative realizations which, albeit inequivalent, are put in correspondence with a subclass of the already classified associative representations for 1D extended supersymmetries. Examples of dynamical systems invariant under octonionic realizations of the extended supersymmetries are given. We cite among the others the octonionic spinning particles, the N = 8 KdV , etc. Possible applications to supersymmetric systems arising from dimensional reduction of the octonionic superstring and M-theory are mentioned.
INFERENCE ANDCOMPUTATION WITHPOPULATIONCODES
Authors: Pouget Alexandre , Dayan Peter , Zemel Richard S.
Published: April 2003

▪ Abstract  In the vertebrate nervous system, sensory stimuli are typically encoded through the concerted activity of large populations of neurons. Classically, these patterns of activity have been treated as encoding the value of the stimulus (e.g., the orientation of a contour), and computation has been formalized in terms of function approximation. More recently, there have been several suggestions that neural computation is akin to a Bayesian inference process, with population activity patterns representing uncertainty about stimuli in the form of probability distributions (e.g., the probability density function over the orientation of a contour). This paper reviews both approaches, with a particular emphasis on the latter, which we see as a very promising framework for future modeling and experimental work.
INSIGHTS INTO THE PATHOGENESIS OF GALACTOSEMIA
Authors: Leslie Nancy D.
Published: April 2003

▪ Abstract  In humans, the absence of galactose-1-phosphate uridyltransferase (GALT) leads to significant neonatal morbidity and mortality which are dependent on galactose ingestion, as well as long-term complications of primary ovarian failure and cognitive dysfunction, which are diet independent. The creation of a knockout mouse model for GALT deficiency was aimed at providing an organism in which metabolic challenges and gene manipulation could address the enigmatic pathophysiologic questions raised by humans with galactosemia. Instead, the mouse represents a biochemical phenotype without evidence of clinical morbidity. The similarities and differences between mice and humans with galactosemia are explored from metabolite, enzyme, and process points of view. The mouse both produces and oxidizes galactose in a manner similar to humans. It differs in brain accumulation of galactitol. Future directions for exploration of this enigmatic condition are discussed.
Revisiting Cauty′s proof of the Schauder conjecture
Authors: Dobrowolski Tadeusz
Published: April 2003

The Schauder conjecture that every compact convex subset of a metric linear space has the fixed‐point property was recently established by Cauty (2001). This paper elaborates on Cauty′s proof in order to make it more detailed, and therefore more
accessible. Such a detailed analysis allows us to show that the convex compacta in metric linear spaces possess the simplicial approximation property introduced by Kalton, Peck, and Roberts. The latter demonstrates that the original Schauder approach to solve the conjecture is in some sense “correctable.”
A Comparison of Encephalization between Odontocete Cetaceans and Anthropoid Primates
Authors: Marino Lori
Published: April 2003

There have been very few studies of brain size and encephalization in cetaceans and essentially none that have made direct quantitative comparisons of cetaceans and another mammalian group using large normative samples. In the present study two different measures of encephalization were calculated and used to rank and compare 21 odontocete species and 60 anthropoid primate species. Comparisons were made both within and between the two groups. Results show that the encephalization level of Homo sapiens is still extraordinary relative to that of nonhuman species. Nevertheless, a subset of delphinid odontocetes are significantly more highly encephalized than the most highly encephalized anthropoid primates and narrow the gap in encephalization between humans and nonhumans substantially. These findings may have implications for comparative models of the relative importance of brain size versus brain organization for the evolution of intelligence.
Somatic and Dendritic Mosaics Formed by Large Ganglion Cells in the Retina of the Common House Gecko (Hemidactylus frenatus)
Authors: Cook Jeremy , Noden Andrew
Published: April 2003

Recent studies of large ganglion cells in fishes and frogs have identified a shared inventory of three basic types, with characteristic forms and spatially independent mosaic distributions. These anamniote types and mosaics are hard to match to the large ganglion cell types and mosaics of mammals, implying that the underlying developmental programmes have diverged during evolution. Reptiles and mammals both belong to the amniote lineage, so the point of divergence can be investigated by comparing the large ganglion cells of reptiles with those of mammals, taking fishes and frogs as outgroups. With this aim, ganglion cells of the common house gecko, Hemidactylus frenatus, were labelled with horseradish peroxidase by an in vitro method and studied in retinal flatmounts. Two prominent, regular, spatially independent mosaics were consistently present. One (αa) was characterized by somata displaced into the inner nuclear layer and dendrites forming planar trees in sublamina a; the other (αab) comprised large orthotopic somata and distinctive, bistratified dendrites that formed discrete planar subtrees in sublaminae a and b. These subtrees were joined by up to 40 vertical link segments, whose distribution was found to correlate with the underlying photoreceptor mosaic. Some specimens also contained patches of a third mosaic (αc), characterized by large orthotopic somata and very large flat trees in sublamina c, but the labelling of this type was inconsistent. These reptilian mosaics share several distinctive characters with anamniote α-cell mosaics but differ markedly from the ganglion cell mosaics of any known mammal. The most parsimonious conclusion is that those mosaic features that are shared by the ganglion cells of all nonmammals are homologous and primitive (symplesiomorphic), while those that are shared by all therian mammals are homologous and derived (synapomorphic). This is consistent with other differences between mammalian and nonmammalian eyes. Mosaic formation itself, however, seems to be a universal characteristic of large ganglion cells.
Prey Selection in the Leopard Frog: Choosing in Biased and Unbiased Situations
Authors: Stull Adrian K. , Gruberg Edward R.
Published: April 2003

When given the option between a ground-level prey presented in front and another prey presented 90° to the side, leopard frogs have a front preference. When given a choice between prey objects presented at the left and right sides, some individual leopard frogs have a side preference. Repeated prey object presentations at one side predispose leopard frogs to respond to the opposite side when presented with prey objects at both sides. The phenomenon is preserved through a half minute delay between single prey presentations (biasing) and two prey presentations (testing) but not through a three-minute delay between biasing and testing. Ten biasing presentations on a side are sufficient to induce opposite side preference, while three biasing presentations are insufficient. Attempts to permanently modify preferences by completely exhausting responsiveness to a single side were unsuccessful. A neural model for the effect of biasing on behavior is shown.
Sexual Dimorphisms in the Brainstem of the Green Anole Lizard
Authors: Wade Juli
Published: April 2003

Male green anoles (Anolis carolinensis) court females by extending a bright red throat fan, called a dewlap. The dewlap is larger in males than in females who do not display the structure in the context of courtship. The ceratohyoid muscle and second ceratobranchial cartilage which control dewlap extension are significantly larger in male than in female anoles. Neurons innervating the ceratohyoid muscle were retrogradely labeled by injecting the muscle with fast blue and were found to be located in the vagal portion of nucleus ambiguus (Amb X), as well as in the region containing the glossopharyngeal portion of nucleus ambiguus (Amb IX) and the ventral portion of the motor nucleus of the facial nerve (nVIImv). Cells in both areas were larger in males than in females. These parallels between structure and function provide the opportunity to study mechanisms of sexual differentiation of brain and behavior.
The Electric Organ Discharge of Brachyhypopomus pinnicaudatus
Authors: Caputi A.A. , Silva A.C. , Macadar O.
Published: April 2003

The electric organ discharge of Brachyhypopomus pinnicaudatus was studied by recording (1) the discharge field potentials in water at different conductivities and temperatures and (2) the spatiotemporal pattern of electromotive forces of the equivalent source. An early deflection, head positive (P wave), and a late deflection, head negative (N wave), are the major components of the discharge, however a striking double positive peak is generated at the abdominal level. Comparisons of this species with other pulse gymnotids provide evidence for common patterns of organization of the electrogenic system: (1) There is a head-to-tail activation wave along the fish; (2) the electromotive force increases exponentially from head to tail, but it is differentially attenuated by the passive tissues in male and females; (3) the abdominal region generates a complex species-specific waveform, whereas the tail discharge is similar across species. In B. pinnicaudatus the electric organ discharge waveform is sensitive to endocrine and environmental stimuli. The effect of seasonal sex differences on electrogenic and passive tissue, the changes in impedance matching between the fish’s body and the environment, and the modulation of membrane properties by temperature, are able to modify the EOD waveform. Since these factors change during the breeding season, their appropriate combination might be crucial for reproduction.
Evolution of Motor Patterns in Tetraodontiform Fishes: Does Muscle Duplication Lead to Functional Diversification?
Authors: Friel John P. , Wainwright Peter C.
Published: April 2003

Several times within the teleost fish order Tetraodontiformes singular jaw adducting muscles have been effectively ‘duplicated’ by physical subdivision to produce new muscles. This morphological system provides an opportunity to investigate how the functional complexity of muscular systems changes with evolutionary increases in the number of component muscles. In this study we asked if muscle duplication has lead to functional diversification by comparing the motor patterns of muscles that result from subdivision events. The activity patterns of five different sets of duplicated muscles were quantified with electromyographic recordings (EMG) from four individuals in each of three species during processing of three prey types. Prey varied in durability and elusiveness (live fiddler crabs, pieces of squid tentacle and live paeneid shrimps). For each cycle of prey processing, measurements were made of the relative onset time of each adductor muscle, the duration of each burst of activity, and the relative intensity of each activity burst. Two types of functional divergence of muscles were observed in analyses of variance conducted on the EMG variables. In two of the 15 variables examined, the timing of activity of the descendant set of muscles differed. In another three of the 15 variables, there were significant interactions between muscle and prey type, indicating a prey effect which differed in the descendant muscles. Overall, evidence of motor divergence was found in three of five cases of muscle duplication. This indicates that muscle subdivision has led to increased functional complexity of the jaw-adductor muscle system in tetraodontiform fishes.
Stepping into the Same River Twice: Homologues as Recurring Attractors in Epigenetic Landscapes
Authors: Striedter Georg F.
Published: April 2003

The reunification of embryology with evolutionary biology is impeded by the perception that a phylogenetic view of homology is incompatible with a developmental approach. This dichotomy disappears when developmental information is viewed not as pre-existing within the zygote but as being constructed during development. Developmental information can be depicted as the surface of an epigenetic landscape. An epigenetic landscape, in turn, can be viewed as a series of aligned energy landscapes that change shape and become more complex as development proceeds. In this view, individual valley bottoms are attractors in state space that tend to reappear reliably in successive generations. Phylogeny can therefore be conceptualized as a succession of epigenetic landscapes, and homologues can be identified as corresponding valleys that have reappeared reliably since their origin in a single ancestral population. Epigenetic homologues can be robust to phylogenetic changes in developmental mechanisms, precursors, and lower level characters. Although application of the epigenetic homology concept is complicated by the lack of explicit information about the topography of epigenetic landscapes, comparative biologists can learn to identify recurring ontogenetic patterns in a manner that is analogous to the identification of input patterns by attractor neural networks. The correspondence of epigenetic valleys is therefore not defined by any essential criteria but by their overlap in multidimensional state space. Whether corresponding valleys are homologous to each other must be determined by a phylogenetic analysis using cladistic methods. Among the general implications of epigenetic homology for comparative neurobiology is that the concept of ‘field homology’ should be used with caution when dealing with novel characters. A case study, applying an epigenetic perspective to understand the variation in monkey visual cortex observed after developmental perturbations, is presented in a final section to make the concept of epigenetic homology more concrete.
Frequency Potentiation in the Medial Cortex of Young Turtle Brains in vitro
Authors: Muñoz M.D. , Magariños-Ascone C. , Gaztelu J.M. , García-Austt E.
Published: April 2003

Turtle brains have a relatively primitive cortex. Glutamate receptors in the cortex of turtles include N-methyl-D-aspartate (NMDA) and DL-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). Our aim was to determine whether the medial cortex in turtles, like the cortex and hippocampus in mammals exhibits frequency potentiation, a non-lasting form of synaptic plasticity, and, if so, to identify the involved receptors. Our results indicate that (1) the medial cortex exhibits this phenomenon with septal stimulation at 2 Hz, the frequency with maximum power spectral density in the electrocorticogram of turtles, showing an increase in both the excitatory postsynaptic potential and the evoked potential amplitudes; (2) the frequency potentiation of the medial cortex in turtles is mediated by AMPA type glutamate receptors; (3) the dynamics of frequency potentiation development in turtles show a number of differences from that in mammals. In summary, the cortex in this group of reptiles exhibits a functional trait of the cortex in mammals that is related to learning and memory; this trait, frequency potentiation, may have appeared as an independent specialization in both groups.
Evolution of the Cerebellum in Primates: Differences in Relative Volume among Monkeys, Apes and Humans
Authors: Rilling James K. , Insel Thomas R.
Published: April 2003

According to the ‘developmental constraint hypothesis’ of comparative mammalian neuroanatomy, brain structures enlarge predictably as the entire brain grows both ontogenetically and phylogenetically. In this study, brain and cerebellum volumes are measured from in vivo magnetic resonance scans of 44 primates from 11 haplorhine species. After controlling for overall brain volume, the cerebellum in both pongid and hylobatid apes is, on average, 45% larger than in monkeys. These results demonstrate that all primate brains are not similarly organized and that developmental constraints are not tight enough to preclude selection for increased cerebellar volume independent of selection on overall brain size.
Different Brain Morphologies from Different Genotypes in a Single Teleost Species, the Medaka (Oryzias latipes)
Authors: Ishikawa Yuji , Yoshimoto Masami , Yamamoto Naoyuki , Ito Hironobu
Published: April 2003

In a teleost fish, the medaka (Oryzias latipes), many inbred strains have been established from various origins including wild populations. Brains from five genetically different strains, which had been bred and raised under the same conditions, were examined to determine whether there is intraspecific genetic variation. A total of 25 brains from the wild-type strains (HNI-II, HB11A and HB32C) and from the body-colour mutant strains (Hi3 and HO5) were fixed, and the external features of the brains were examined under a stereomicroscope. The differences between the HNI-II brains and the Hi3 brains were the most remarkable in the external features. In order to carry out a volumetric analysis, the brains of all strains were cut into complete serial cryostat sections. Total brain volumes and relative volumes (in % of total brain volume) of the olfactory bulb, telencephalon, optic tectum, and cerebellum were calculated in each brain using a semi-automatic image analyzer. Statistical analysis showed that significant differences in the total brain volumes and the relative volumes of these subdivisions exist not only between wild-type and mutant strains but also among wild-type strains. Thus, our results demonstrate that the strains with different genotypes possess large variation in brain morphology. This is the first report to demonstrate that there exists intraspecific genetic variation in the gross brain morphology of a wild-type vertebrate.
Retinal Projections and Retinal Ganglion Cell Distribution Patterns in a Sturgeon (Acipenser transmontanus), a Non-Teleost Actinopterygian Fish
Authors: Ito Hironobu , Yoshimoto Masami , Albert James S. , Yamamoto Naoyuki , Sawai Nobuhiko
Published: April 2003

Retinal projections in a sturgeon were studied by injecting biocytin or HRP into the optic nerve. The target areas are the preoptic area, thalamus, area pretectalis, nucleus of posterior commissure, optic tectum, and nuclei of the accessory optic tract. Furthermore, a few labeled fibers and terminals were found in a ventrolateral area of the caudal telencephalon. All retinal projections are bilateral, although contralateral projections were more heavily labeled. Retrogradely labeled neurons were found in the ventral thalamus bilaterally. Retinal projections in sturgeons are similar to those of other non-teleost actinopterygians and chondrichthyans (sharks), in terms of the targets and extent of bilateral projections. Distribution patterns of ganglion cells in the retina were examined in Nissl-stained retinal whole mount preparations. The highest density areas were found in the temporal and nasal retinas, and a dense band of ganglion cells was observed along the horizontal axis between the nasal and temporal areas of highest density. The density of ganglion cells in the dorsal retina is the lowest. The total number of ganglion cells was estimated to be about 5 × 104 in a retina. The existence of a low density area in the dorsal retina suggests reduced visual acuity in the ventral visual field.
Calcium Binding Protein Immunoreactivity in Nucleus Rotundus in a Reptile, Caiman crocodilus
Authors: Pritz Michael B. , Siadati Abdolreza
Published: April 2003

Nucleus rotundus is a prominent nucleus in the dorsal thalamus of nonmammalian amniotes. In one group of reptiles, Caiman crocodilus, previous studies have identified three parts of this neuronal aggregate. The central portion, the rotundal core, which receives visual input from the midbrain and projects to a restricted portion of the telencephalon, contains relay cells only. Previous examinations using Nissl morphology indicated that neurons of the rotundal core were not a homogeneous population of cells. The present investigation utilized another methodology to examine cell populations within the rotundal core, immunoreactivity to the calcium binding proteins, calbindin/calretinin and parvalbumin. Light microscopic observations revealed the following features. First, calbindin/calretinin immunoreactive neurons and parvalbumin immunoreactive neurons were present in the rotundal core. Of these two antibodies, immunoreactivity to calbindin/calretinin was much more robust and calbindin/calretinin immunoreactive neurons were more numerous than parvalbumin cells. Second, neurons immunoreactive to either calbindin/calretinin or parvalbumin were not homogeneous but comprised several populations based on perikaryal shape and size and neuronal process morphology. These results are compared with similar data in other amniotes.
Immunohistochemical Localization of NMDA- and AMPA-Type Glutamate Receptor Subunits in the Basal Ganglia of Red-Eared Turtles
Authors: Fowler Michael , Medina Loreta , Reiner Anton
Published: April 2003

Corticostriatal and thalamostriatal projection systems have been shown to utilize glutamate as a neurotransmitter in mammals and birds. Although corticostriatal and thalamostriatal projection systems have been demonstrated in turtles, it is uncertain whether they too use glutamate as their neurotransmitter. Immunohistochemical localization of glutamate and of NMDA- and AMPA-type ionotropic glutamate receptor subunits (NMDAR2A/B, GluR1, GluR2/3, and GluR4) were used to address this issue. Numerous medium-sized neurons that were rich in NMDAR2A/B and GluR2/3 were observed in the striatal part of the basal ganglia of red-eared turtles. Smaller numbers of medium-sized neurons and some large neurons rich in the GluR1 and GluR4 subunits were also observed in the striatum. The striatal neuropil was notably rich in GluR1, GluR2/3 and NMDAR2A/B subunits. The pallidal region was specifically rich in large neurons possessing GluR4 subunits. Consistent with the glutamate receptors on striatal and pallidal neurons, sources of input to the striatum and pallidum in turtle such as the dorsomedial and dorsolateral thalamic nuclei (which appear to correspond to intralaminar thalamic nuclei), telencephalic pallial cell groups, and the apparent subthalamic nucleus homologue were rich in glutamatergic neurons. The results show that the thalamostriatal, corticostriatal and subthalamo-pallidal projection systems of turtles are glutamatergic and that similar basal ganglia cell types in turtles and mammals have largely similar glutamate receptor characteristics.
Immunocytochemical Localization of Gonadotropin-Releasing Hormones in the Brain of a Viviparous Caecilian Amphibian, Typhlonectes natans (Amphibia: Gymnophiona)
Authors: Ebersole Ted J. , Boyd Sunny K.
Published: April 2003

The molecular forms and brain distribution of gonadotropin-releasing hormone (GnRH) have been well studied in the amphibian orders Urodela (salamanders and newts) and Anura (frogs and toads). In the order Gymnophiona (caecilians), however, few species have been investigated. Antibodies against different molecular forms of GnRH were used to immunohistochemically localize the GnRH-containing neurons in the brain of the caecilian, Typhlonectes natans which differs from most other amphibians in that it is viviparous. An antibody selective for mammalian GnRH recognized cell bodies predominantly in the septo-preoptic area but only with occasional cell bodies in the lateral hypothalamus and ventral thalamic eminence. Thick, prominent fibers in the septal region and fibers within the terminal nerve were also labeled. An antibody selective for chicken-II GnRH labeled a population of cell bodies in the dorsal hypothalamus, ventral thalamus and midbrain tegmentum. Thin fibers projected laterally from these cells. An antibody specific for salmon GnRH did not label cell bodies but did show intense terminal field immunoreactivity. The brain of this caecilian, therefore, contains three antigenically distinct forms of GnRH. The mammalian and chicken-II GnRH peptides have been shown in other amphibians but the distribution of cells and fibers was unique in this caecilian.
Hypothalamic Arginine Vasotocin mRNA Abundance Variation Across Sexes and with Sex Change in a Coral Reef Fish
Authors: Godwin John , Sawby Ryan , Warner Robert R. , Crews David , Grober Matthew S.
Published: April 2003

Gonadal hormones are important mediators of sexual and aggressive behavior in vertebrates. Recent evidence suggests that the peptide hormones arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) often critically mediate these gonadal hormone effects on behavior and have direct influences on behavioral variation. Behavioral differences between sexes, across reproductive states, and even among closely related species are correlated with differences in central AVT/AVP systems in many species. We report differences in hypothalamic AVT mRNA levels between distinct alternate male phenotypes and with female-to-male sex change in the bluehead wrasse (Thalassoma bifasciatum), a teleost fish. The aggressively dominant and strongly courting male phenotype has greater numbers of AVT mRNA producing cells in the magnocellular preoptic area of the hypothalamus than females. Levels of AVT mRNA within these cells in dominant males are also approximately three times female levels whereas the non-aggressive male phenotype has AVT mRNA levels approximately twice female levels. Behavioral sex change is very rapid in this species and is not dependent on the presence of gonads. Conversely, rapid increases in sexual and aggressive behavior during sex change are closely paralleled by approximate fourfold increases in hypothalamic AVT-mRNA levels. The behavioral plasticity shown by bluehead wrasses in response to social environment might be mediated in part by a neuropeptide, AVT, with changes in the gonads and gonadal hormones as the result rather than the cause of behavioral dominance.
The Interneurons of the Abdominal Positioning System of the Crayfish
Authors: Larimer James L.
Published: April 2003

Arthropods with segmented abdomens show similar abdominal positioning behaviors. It has been possible to gain some understanding of the neural basis of these behaviors in lobsters and crayfish using standard intracellular and dye-filling techniques. Typically crayfish and lobsters have six abdominal segments each controlled by a set of flexor and extensor tonic muscles. Each segment has a dozen tonic motor neurons controlled in turn by a large number of interneurons. A similar set of phasic muscles, motor neurons and interneurons control a fast system. The fast components underlie such behaviors as escape and swimming. Lucifier-filled microelectrodes were used to stimulate, record and dye-fill the motor neurons and interneurons of the tonic systems. It was soon apparent that all of these neurons are identifiable. These data allowed us to determine how many interneurons served in a circuit generating a behavior, while the use of pairs of electrodes permitted the study of synaptic interactions between interneurons. Interneurons involved in abdominal positioning produced either flexion (flexion producing interneurons or FPI), extension (EPI) or inhibition (I). Significantly, FPIs tended to synaptically excite other FPIs and inhibit EPIs. In turn EPIs excited other EPIs and inhibited FPIs. As a result, impaling and stimulating an FPI, for example, tended to recruit others and their combined activity evoked a natural-looking behavior. The inhibition between FPI and EPI and vice versa tended to account for the reciprocity seen between the two behaviors in all experiments. Finally the synaptic connections between EPI–EPI on FPI–FPI were found to be essentially invariable. Thus repeated stimulation of an FPI or the stimulation of this same FPI in another preparation, at another time, gave essentially the same overall behavior such that the stimulation of one FPI or EPI could evoke a wide spread output resembling a normal behavior.
Network Architectures and Circuit Function: Testing Alternative Hypotheses in Multifunctional Networks
Authors: Leonard Janet L.
Published: April 2003

Understanding how species-typical movement patterns are organized in the nervous system is a central question in neurobiology. The current explanations involve ‘alphabet’ models in which an individual neuron may participate in the circuit for several behaviors but each behavior is specified by a specific neural circuit. However, not all of the well-studied model systems fit the ‘alphabet’ model. The ‘equation’ model provides an alternative possibility, whereby a system of parallel motor neurons, each with a unique (but overlapping) field of innervation, can account for the production of stereotyped behavior patterns by variable circuits. That is, it is possible for such patterns to arise as emergent properties of a generalized neural network in the absence of feedback, a simple version of a ‘self-organizing’ behavioral system. Comparison of systems of identified neurons suggest that the ‘alphabet’ model may account for most observations where CPGs act to organize motor patterns. Other well-known model systems, involving architectures corresponding to feed-forward neural networks with a hidden layer, may organize patterned behavior in a manner consistent with the ‘equation’ model. Such architectures are found in the Mauthner and reticulospinal circuits, ‘escape’ locomotion in cockroachs, CNS control of Aplysia gill, and may also be important in the coordination of sensory information and motor systems in insect mushroom bodies and the vertebrate hippocampus. The hidden layer of such networks may serve as an ‘internal representation’ of the behavioral state and/or body position of the animal, allowing the animal to fine-tune oriented, or particularly context-sensitive, movements to the prevalent conditions. Experiments designed to distinguish between the two models in cases where they make mutually exclusive predictions provide an opportunity to elucidate the neural mechanisms by which behavior is organized in vivo and in vitro.
Colocalization of Neuronal NO Synthase with Urotensins I and II in the Caudal Neurosecretory Neurons and the Urophysis of the Teleost Oreochromis niloticus
Authors: Cioni Carla , De Vito Luana
Published: April 2003

The intracellular distribution of neuronal nitric oxide synthase (nNOS) was studied in the caudal neurosecretory system of a teleost, Oreochromis niloticus (Cichlids), by means of post-embedding immunogold labeling with a polyclonal antibody directed against nNOS of human origin. Ultrastructural examination demonstrated that neuronal NOS-like molecules are distributed within the Dahlgren cell perikarya, the neurosecretory axons, and the urophysial axon terminals. In the neurosecretory somata, gold particles for nNOS were mainly cytosolic, whereas in the neurosecretory axons and axon terminals they were associated with the membrane and/or the dense core of neurosecretory granules. Double immunogold labelings for nNOS/urotensin I (UI) and nNOS/urotensin II (UII) demonstrated that nNOS-like molecules are colocalized with UI and/or UII in the neurosecretory granules contained within the urophysial terminals. The present findings suggest that both a soluble cytosolic and a particulate neuronal NOS are expressed in the caudal neurosecretory neurons. They confirm previous biochemical data on the same species.
Angina pectoris in Severe Aortic Stenosis
Authors: Dangas George , Khan Sultan , Curry Bryan H. , Kini Annapoorna S. , Sharma Samin K.
Published: April 2003

We studied the value of angina pectoris as a predictor of significant coronary artery disease (CAD) in very elderly patients with severe aortic stenosis (AS). The study population consisted of patients with age at least 70 years who were referred for balloon aortic valvuloplasty (n = 90 patients). Routine coronary angiography was performed before the valvular intervention. Patients were grouped according to the presence or absence of angina pectoris. Of the patients with angina pectoris, 78% had obstructive (>50% diameter stenosis) CAD on coronary angiogram, while only 17% of patients without angina pectoris had obstructive CAD (p < 0.01). Angina pectoris had a sensitivity of 78% and a specificity of 82% for prediction of obstructive CAD. This suggests that in elderly patients with severe AS, the presence of angina pectoris is a strong determinant of CAD, and the absence of angina strongly suggests absence of obstructive CAD. In a very elderly population, appropriate decision-making with respect to AS management should not await diagnostic coronary angiography.
Transvenous Pacemaker Leads Do Not Worsen Tricuspid Regurgitation: A Prospective Echocardiographic Study
Authors: Leibowitz David W. , Rosenheck Shimon , Pollak Arthur , Geist Michael , Gilon Dan
Published: April 2003

Limited prospective data are available regarding the influence of pacemaker leads on tricuspid valve function. To examine the true incidence of these complications, 35 patients were prospectively examined by two-dimensional and Doppler echocardiography before and after implantation of either a permanent pacemaker or an automatic implantable cardioverter-defibrillator. Of the 35 patients imaged preoperatively, the amount of tricuspid regurgitation (TR) was judged as normal or trivial in 15 (43%), mild in 10 (29%), moderate in 8 (23%), and severe in 2 (6%). Following electrode implantation, TR was noted to be normal or trivial in 13 (38%), mild in 15 (48%), moderate in 6 (17%) and severe in 1 (3%). We conclude that implantation of permanent right ventricular electrodes is not usually associated with an acute worsening of tricuspid regurgitation in most patients.