bluuebunny/crossref_metadata_2025 huggingface dataset:
MYST Family Histone Acetyltransferases in the Protozoan Parasite
Toxoplasma gondii
Authors: Smith Aaron T. , Tucker-Samaras Samantha D. , Fairlamb Alan H. , Sullivan William J.
Published: December 2005

The restructuring of chromatin precedes tightly regulated events such as DNA transcription, replication, and repair. One type of chromatin remodeling involves the covalent modification of nucleosomes by histone acetyltransferase (HAT) complexes. The observation that apicidin exerts antiprotozoal activity by targeting a histone deacetyltransferase has prompted our search for more components of the histone modifying machinery in parasitic protozoa. We have previously identified GNAT family HATs in the opportunistic pathogen
Toxoplasma gondii
and now describe the first MYST (named for members MOZ, Ybf2/Sas3, Sas2, and Tip60) family HATs in apicomplexa (TgMYST-A and -B). The TgMYST-A genomic locus is singular and generates a ∼3.5-kb transcript that can encode two proteins of 411 or 471 amino acids. TgMYST-B mRNA is ∼7.0 kb and encodes a second MYST homologue. In addition to the canonical MYST HAT catalytic domain, both TgMYST-A and -B possess an atypical C2HC zinc finger and a chromodomain. Recombinant TgMYST-A exhibits a predilection to acetylate histone H4 in vitro at lysines 5, 8, 12, and 16. Antibody generated to TgMYST-A reveals that both the long and short (predominant) versions are present in the nucleus and are also plentiful in the cytoplasm. Moreover, both TgMYST-A forms are far more abundant in rapidly replicating parasites (tachyzoites) than encysted parasites (bradyzoites). A bioinformatics survey of the
Toxoplasma
genome reveals numerous homologues known to operate in native MYST complexes. The characterization of TgMYST HATs represents another important step toward understanding the regulation of gene expression in pathogenic protozoa and provides evolutionary insight into how these processes operate in eukaryotic cells in general.
Gene Set Coregulated by the
Saccharomyces cerevisiae
Nonsense-Mediated mRNA Decay Pathway
Authors: Taylor Rachel , Kebaara Bessie Wanja , Nazarenus Tara , Jones Ashley , Yamanaka Rena , Uhrenholdt Rachel , Wendler Jason P. , Atkin Audrey L.
Published: December 2005

The nonsense-mediated mRNA decay (NMD) pathway has historically been thought of as an RNA surveillance system that degrades mRNAs with premature translation termination codons, but the NMD pathway of
Saccharomyces cerevisiae
has a second role regulating the decay of some wild-type mRNAs. In
S. cerevisiae
, a significant number of wild-type mRNAs are affected when NMD is inactivated. These mRNAs are either wild-type NMD substrates or mRNAs whose abundance increases as an indirect consequence of NMD. A current challenge is to sort the mRNAs that accumulate when NMD is inactivated into direct and indirect targets. We have developed a bioinformatics-based approach to address this challenge. Our approach involves using existing genomic and function databases to identify transcription factors whose mRNAs are elevated in NMD-deficient cells and the genes that they regulate. Using this strategy, we have investigated a coregulated set of genes. We have shown that NMD regulates accumulation of
ADR1
and
GAL4
mRNAs, which encode transcription activators, and that Adr1 is probably a transcription activator of
ATS1
. This regulation is physiologically significant because overexpression of
ADR1
causes a respiratory defect that mimics the defect seen in strains with an inactive NMD pathway. This strategy is significant because it allows us to classify the genes regulated by NMD into functionally related sets, an important step toward understanding the role NMD plays in the normal functioning of yeast cells.
Enzymes of the Heme Biosynthetic Pathway in the Nonphotosynthetic Alga
Polytomella
sp
Authors: Atteia Ariane , van Lis Robert , Beale Samuel I.
Published: December 2005

Heme
biosynthesis involves a number of enzymatic steps which in eukaryotes
take place in different cell compartments. Enzyme compartmentalization
differs between photosynthetic and nonphotosynthetic eukaryotes. Here
we investigated the structures and subcellular localizations of three
enzymes involved in the heme pathway in
Polytomella
sp., a
colorless alga evolutionarily related to the green alga
Chlamydomonas reinhardtii
. Functional complementation of
Escherichia coli
mutant strains was used to isolate cDNAs
encoding three heme biosynthetic enzymes, glutamate-1-semialdehyde
aminotransferase, protoporphyrinogen IX oxidase, and ferrochelatase.
All three proteins show highest similarity to their counterparts in
photosynthetic organisms, including
C. reinhardtii
. All three
proteins have N-terminal extensions suggestive of intracellular
targeting, and immunoblot studies indicate their enrichment in a dense
cell fraction that is enriched in amyloplasts. These results suggest
that even though the plastids of
Polytomella
sp. are not
photosynthetically active, they are the major site of heme
biosynthesis. The presence of a gene for glutamate-1-semialdehyde
aminotransferase suggests that
Polytomella
sp. uses the
five-carbon pathway for synthesis of the heme precursor
5-aminolevulinic
acid.
Sequencing of Random
Euplotes crassus
Macronuclear Genes Supports a High Frequency of +1 Translational Frameshifting
Authors: Klobutcher Lawrence A.
Published: December 2005

Programmed translational frameshifts have been identified in genes from a broad range of organisms, but typically only a very few genes in a given organism require a frameshift for expression. In contrast, a recent analysis of gene sequences available in GenBank from ciliates in the genus
Euplotes
indicated that >5% required one or more +1 translational frameshifts to produce their predicted protein products. However, this sample of genes was nonrandom, biased, and derived from multiple
Euplotes
species. To test whether there truly is an abundance of frameshift genes in
Euplotes
, and to more accurately assess their frequency, we sequenced a random sample of 25 cloned genes/macronuclear DNA molecules from
Euplotes crassus
. Three new candidate +1 frameshift genes were identified in the sample that encode a membrane occupation and recognition nexus (MORN) repeat protein, a C
2
H
2
-type zinc finger protein, and a Ser/Thr protein kinase. Reverse transcription-PCR analyses indicate that all three genes are expressed in vegetatively proliferating cells and that the mRNAs retain the requirement of a frameshift. Although the sample of sequenced genes is relatively small, the results indicate that the frequency of genes requiring frameshifts in
E. crassus
is between 3.7% and 31.7% (at a 95% confidence interval). The current and past data also indicate that frameshift sites are found predominantly in genes that likely encode nonabundant proteins in the cell.
RNA-Binding Domain Proteins in Kinetoplastids: a Comparative Analysis
Authors: De Gaudenzi Javier , Frasch Alberto C. , Clayton Christine
Published: December 2005

RNA-binding proteins are important in many aspects of RNA processing, function, and destruction. One class of such proteins contains the RNA recognition motif (RRM), which consists of about 90 amino acid residues, including the canonical RNP1 octapeptide: (K/R)G(F/Y)(G/A)FVX(F/Y). We used a variety of homology searches to classify all of the RRM proteins of the three kinetoplastids
Trypanosoma brucei
,
Trypanosoma cruzi
, and
Leishmania major
. All three organisms have similar sets of RRM-containing protein orthologues, suggesting common posttranscriptional processing and regulatory pathways. Of the 75 RRM proteins identified in
T. brucei
, only 13 had clear homologues in other eukaryotes, although 8 more could be given putative functional assignments. A comparison with the 18 RRM proteins of the obligate intracellular parasite
Encephalitozoon cuniculi
revealed just 3 RRM proteins which appear to be conserved at the primary sequence level throughout eukaryotic evolution: poly(A) binding protein, the rRNA-processing protein MRD1, and the nuclear cap binding protein.
Nd6p, a Novel Protein with RCC1-Like Domains Involved in Exocytosis in
Paramecium tetraurelia
Authors: Gogendeau Delphine , Keller Anne-Marie , Yanagi Akira , Cohen Jean , Koll France
Published: December 2005

In
Paramecium tetraurelia
, the regulated secretory pathway of dense core granules called trichocysts can be altered by mutation and genetically studied. Seventeen nondischarge (ND) genes controlling exocytosis have already been identified by a genetic approach. The site of action of the studied mutations is one of the three compartments, the cytosol, trichocyst, or plasma membrane. The only ND genes cloned to date correspond to mutants affected in the cytosol or in the trichocyst compartment. In this work, we investigated a representative of the third compartment, the plasma membrane, by cloning the
ND6
gene. This gene encodes a 1,925-amino-acid protein containing two domains homologous to the regulator of chromosome condensation 1 (RCC1). In parallel, 10 new alleles of the
ND6
gene were isolated. Nine of the 12 available mutations mapped in the RCC1-like domains, showing their importance for the Nd6 protein (Nd6p) function. The RCC1 protein is well known for its guanine exchange factor activity towards the small GTPase Ran but also for its involvement in membrane fusion during nuclear envelope assembly. Other proteins with RCC1-like domains are also involved in intracellular membrane fusion, but none has been described yet as involved in exocytosis. The case of Nd6p is thus the first report of such a protein with a documented role in exocytosis.
The Plasmodial Surface Anion Channel Is Functionally Conserved in Divergent Malaria Parasites
Authors: Lisk Godfrey , Desai Sanjay A.
Published: December 2005

The plasmodial surface anion channel (PSAC), a novel ion channel induced on human erythrocytes infected with
Plasmodium falciparum
, mediates increased permeability to nutrients and presumably supports intracellular parasite growth. Isotope flux studies indicate that other malaria parasites also increase the permeability of their host erythrocytes, but the precise mechanisms are unknown. Channels similar to PSAC or alternative mechanisms, such as the upregulation of endogenous host transporters, might fulfill parasite nutrient demands. Here we evaluated these possibilities with rhesus monkey erythrocytes infected with
Plasmodium knowlesi
, a parasite phylogenetically distant from
P. falciparum
. Tracer flux and osmotic fragility studies revealed dramatically increased permeabilities paralleling changes seen after
P. falciparum
infection. Patch-clamp of
P. knowlesi
-infected rhesus erythrocytes revealed an anion channel with striking similarities to PSAC: its conductance, voltage-dependent gating, pharmacology, selectivity, and copy number per infected cell were nearly identical. Our findings implicate a family of unusual anion channels highly conserved on erythrocytes infected with various malaria parasites. Together with PSAC's exposed location on the host cell surface and its central role in transport changes after infection, this conservation supports development of antimalarial drugs against the PSAC family.
Ascospore Formation in the YeastSaccharomyces cerevisiae
Authors: Neiman Aaron M.
Published: December 2005

Sporulation of the baker's yeastSaccharomyces cerevisiaeis a response to nutrient depletion that allows a single diploid cell to give rise to four stress-resistant haploid spores. The formation of these spores requires a coordinated reorganization of cellular architecture. The construction of the spores can be broadly divided into two phases. The first is the generation of new membrane compartments within the cell cytoplasm that ultimately give rise to the spore plasma membranes. Proper assembly and growth of these membranes require modification of aspects of the constitutive secretory pathway and cytoskeleton by sporulation-specific functions. In the second phase, each immature spore becomes surrounded by a multilaminar spore wall that provides resistance to environmental stresses. This review focuses on our current understanding of the cellular rearrangements and the genes required in each of these phases to give rise to a wild-type spore.
Comparative Genomic Analyses of the Bacterial Phosphotransferase System
Authors: Barabote Ravi D. , Saier Milton H.
Published: December 2005

We
report analyses of 202 fully sequenced genomes for homologues of known
protein constituents of the bacterial phosphoenolpyruvate-dependent
phosphotransferase system (PTS). These included 174 bacterial, 19
archaeal, and 9 eukaryotic genomes. Homologues of PTS proteins were not
identified in archaea or eukaryotes, showing that the horizontal
transfer of genes encoding PTS proteins has not occurred between the
three domains of life. Of the 174 bacterial genomes (136 bacterial
species) analyzed, 30 diverse species have no PTS homologues, and 29
species have cytoplasmic PTS phosphoryl transfer protein homologues but
lack recognizable PTS permeases. These soluble homologues presumably
function in regulation. The remaining 77 species possess all PTS
proteins required for the transport and phosphorylation of at least one
sugar via the PTS. Up to 3.2% of the genes in a bacterium encode PTS
proteins. These homologues were analyzed for family association, range
of protein types, domain organization, and organismal distribution.
Different strains of a single bacterial species often possess
strikingly different complements of PTS proteins. Types of PTS protein
domain fusions were analyzed, showing that certain types of domain
fusions are common, while others are rare or prohibited. Select PTS
proteins were analyzed from different phylogenetic standpoints, showing
that PTS protein phylogeny often differs from organismal phylogeny. The
results document the frequent gain and loss of PTS protein-encoding
genes and suggest that the lateral transfer of these genes within the
bacterial domain has played an important role in bacterial evolution.
Our studies provide insight into the development of complex
multicomponent enzyme systems and lead to predictions regarding the
types of protein-protein interactions that promote efficient
PTS-mediated phosphoryl transfer.
Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus
Authors: Weiss Susan R. , Navas-Martin Sonia
Published: December 2005

Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses classified within the Nidovirales order. This coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (SARS-CoV). This review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses the newly described human emerging pathogen, SARS-CoV. The coronavirus part covers (i) a description of a group of coronaviruses and the diseases they cause, including the prototype coronavirus, murine hepatitis virus, which is one of the recognized animal models for multiple sclerosis, as well as viruses of veterinary importance that infect the pig, chicken, and cat and a summary of the human viruses; (ii) a short summary of the replication cycle of coronaviruses in cell culture; (iii) the development and application of reverse genetics systems; and (iv) the roles of individual coronavirus proteins in replication and pathogenesis. The SARS-CoV part covers the pathogenesis of SARS, the developing animal models for infection, and the progress in vaccine development and antiviral therapies. The data gathered on the animal coronaviruses continue to be helpful in understanding SARS-CoV.
ON THE RELATIONSHIP BETWEEN SIGMA MODELS AND SPIN CHAINS
Authors: CONTROZZI D. , HAWKINS E.
Published: December 2005

We consider the two-dimensional O (3) non-linear sigma model with topological term using a lattice regularization introduced by Shankar and Read [Nucl. Phys. B336, 457 (1990)], that is suitable for studying the strong coupling regime. When this lattice model is quantized, the coefficient θ of the topological term is quantized as θ=2πs, with s integer or half-integer. We study in detail the relationship between the low energy behaviour of this theory and the one-dimensional spin-s Heisenberg model. We generalize the analysis to sigma models with other symmetries.
X-RAY MAGNETIC CIRCULAR DICHROISM ON Pt L-EDGES IN Co-BASED MATERIALS
Authors: POULOPOULOS P.
Published: December 2005

Progress in third-generation synchrotron radiation facilities has made possible, nowadays, the determination of induced spin and orbital magnetic moments of 5d transition metal elements via the element-specific X-ray magnetic circular dichroism technique. In this work, recent results on the magnetic moments of Pt in Co -based alloys and multilayers are briefly reviewed. The magnetic moment carried by the 5d electrons of Pt in these systems ranges between 0.2 and 0.7μ B /atom. The ratio of orbital μ L to spin μS magnetic moment is found to be in the range 0.15–0.25. Finally, a method is described for the determination of Pt magnetic moment in lattices other than the fcc lattice, which is the thermodynamically stable crystallographic structure of bulk Pt .
A METHODOLOGY FOR TRACKING SOLUTE DISTRIBUTION IN A MATHEMATICAL MODEL OF THE KIDNEY
Authors: LAYTON ANITA T.
Published: December 2005

The goal of this study is to develop a methodology for tracking the distribution of filtered solute in mathematical models of the urine concentrating mechanism. Investigation of intrarenal solute distribution, and its cycling by way of countercurrent exchange and preferential tubular interactions, may yield new insights into fundamental principles of concentrating mechanism function. Our method is implemented in a dynamic formulation of a central core model that represents renal tubules in both the cortex and the medulla. Axial solute diffusion is represented in intratubular flows and in the central core. By representing the fate of solute originally belonging to a marked bolus, we obtain the distribution of that solute as a function of time. In addition, we characterize the residence time of that solute by computing the portion of that solute remaining in the model system as a function of time. Because precise mass conservation is of particular importance in solute tracking, our numerical approach is based on the second-order Godunov method, which, by construction, is mass-conserving and accurately represents steep gradients and discontinuities in solute concentrations and tubular properties.
MODELING INFECTIOUS DISEASES USING GLOBAL STOCHASTIC CELLULAR AUTOMATA
Authors: MIKLER ARMIN R. , VENKATACHALAM SANGEETA , ABBAS KAJA
Published: December 2005

Susceptibles-infectives-removals (SIR) and its derivatives are the classic mathematical models for the study of infectious diseases in epidemiology. In order to model and simulate epidemics of an infectious disease, we use cellular automata (CA). The simplifying assumptions of SIR and naive CA limit their applicability to the real world characteristics. A global stochastic cellular automata paradigm (GSCA) is proposed, which incorporates geographic and demographic based interactions. The interaction measure between the cells is a function of population density and Euclidean distance, and has been extended to include geographic, demographic and migratory constraints. The progression of diseases using traditional CA and classic SIR are analyzed, and similar behavior to the SIR model is exhibited by GSCA, using the geographic information systems (GIS) gravity model for interactions. The limitations of the SIR and naive CA models of homogeneous population with uniform mixing are addressed by the GSCA model. The GSCA model is oriented to heterogeneous population, and can incorporate interactions based on geography, demography, environment and migration patterns. The progression of diseases can be modeled at higher levels of fidelity using the GSCA model, and facilitates optimal deployment of public health resources for prevention, control and surveillance of infectious diseases.
ASCERTAINING HIV UNDERREPORTING IN LOW PREVALENCE COUNTRIES USING THE APPROXIMATE RATIO OF UNDERREPORTING
Authors: HSIEH YING-HEN , WANG HUI-CHING , DE ARAZOZA HECTOR , LOUNES RACHID , TWU SHIING-JER , HSU HSU-MEI
Published: December 2005

Underreporting of HIV/AIDS cases is a common problem in HIV epidemiology which often skews epidemiologic projections on which public health policy decisions are often based, especially in the cases of low HIV prevalence countries or in early phases of an emerging epidemic when the HIV incidence is still low, but might be growing rapidly. In this work, we propose a simple mathematical model with groups of known and undetected HIV-positives. Using this model with the annual HIV incidence data of new HIV cases and new AIDS cases detected at onset of symptoms, we are able to obtain an estimate for the number of undetected HIV-positives. Moreover, using Taiwan data of 1993–2000, we are able to predict the number of new cases in the next two years within 5% accuracy. We also give an approximate ratio of underreporting which approximates the magnitude of underreporting of HIV cases in low HIV prevalence settings. The procedure is illustrated with the HIV data of Taiwan and Cuba. The result shows that underreporting in Cuba is low, probably due to its intense contact tracing program. For Taiwan, the level of underreporting is higher, but has improved slightly since 1999. The method is useful as a simple tool to gauge the immediate impact of an emerging epidemic, as well as for the purpose of public health policy planning and short-term future projections.
EMPIRICAL STUDY OF SUPPLIER SELECTION PRACTICES IN SUPPLY CHAIN MANAGEMENT IN MANUFACTURING COMPANIES
Authors: WANG DAN , TIAN YEZHUANG , HU YUNQUAN
Published: December 2005

Supply chain management has seen a wide application since the 1990s in satisfying diversified customer demands. To remain competitive on a global scale, manufacturing companies greatly increased the scope of their outsourcing activities. Consequently, supplier selection has become a highly prioritized activity with major significance to companies. Previous studies of supplier selection show that there are commonly accepted supplier selection criteria. However, there are insufficient studies on the association between the manufacturer's criteria of supplier selection and why it wins orders from its customers. Studies on the differences of supplier selection criteria among manufacturers from different countries are insufficient either. Through empirical study this paper tries to find out the association between manufacturer's criteria in supplier selection and how it wins orders. Considerations of supplier selection criteria in different national background are compared and the consistency of supplier selection criteria and competitive priority is analyzed.
EVALUATING THE LONG-TERM BENEFIT OF CRM-SYSTEMS: A COST-ORIENTED APPROACH
Authors: MOEDRITSCHER GERNOT , MUSSNIG WERNER
Published: December 2005

Since the late 1990s Customer Relationship Management (CRM) has become a buzzword especially among business practitioners and consultants. Companies have invested or are planning to invest huge amounts to implement CRM strategies, tools and infrastructure in order to win the battle in the increasingly competitive economy. However, many executives are struggling to determine how their enterprises will balance the business value of CRM against its costs to determine CRM return on investment. Our model presented in this paper allows an adequate feasible, theoretically established prospective evaluation for the contribution of a CRM-investment to the value of the firm under cost aspects. The premise for the application of this model is that strategic concepts, a fully developed cost accounting system as well as information on the part of the market are available. However, at the present in companies it is still not common to use such integrated and dynamic models. But an essential barrier of the implementation is the mindset of the management, which is stamped by conventions like e.g. orientation on financial statements or pursuit of partial orientation.
COMMERCIAL ASPECTS OF CONVERGED TELECOM-BROADCASTING SERVICE: INSIGHTS FROM THE SATELLITE DMB SERVICE IN KOREA
Authors: SAWNG YEONG-WHA , HAN HYUN-SOO
Published: December 2005

One of the dominant trends in Korea's IT industry of late is digital convergence. Of all forms of digital convergence, the one between telecommunications and broadcasting in the form of satellite DMB (Digital Media Broadcasting) service is regarded as the most innovative, and it is eliciting interest from a technological and regulatory viewpoint, as well as from a business model perspective. In this paper, as an exemplary case study, we describe the distinctive characteristics of satellite DMB service, forecast market acceptance for satellite DMB service and provide quantified estimation results. The focus of the study is on gauging how successful is the market debut for this leading convergence service. The paper also examines other services of similar type, subject to the same regulations, for comparative purposes, and the estimation of the market acceptance for satellite DMB service which draws on theories of innovation diffusion. Satellite DMB service, being one of the culminations of the telecom-broadcasting convergence initiatives of recent times (the findings of this study, as has been confirmed by recent Korean experiences) can be useful for further research on similar digital convergence service products.
COMPUTER-BASED DESIGN OF NOVEL PROTEIN STRUCTURES
Authors: Butterfoss Glenn L. , Kuhlman Brian
Published: December 2005

Over the past 10 years there has been tremendous success in the area of computational protein design. Protein design software has been used to stabilize proteins, solubilize membrane proteins, design intermolecular interactions, and design new protein structures. A key motivation for these studies is that they test our understanding of protein energetics and structure. De novo design of novel structures is a particularly rigorous test because the protein backbone must be designed in addition to the amino acid side chains. A priori it is not guaranteed that the target backbone is even designable. To address this issue, researchers have developed a variety of methods for generating protein-like scaffolds and for optimizing the protein backbone in conjunction with the amino acid sequence. These protocols have been used to design proteins from scratch and to explore sequence space for naturally occurring protein folds.
Norepinephrine-induced oxidative stress causes PC-12 cell apoptosis by both endoplasmic reticulum stress and mitochondrial intrinsic pathway: inhibition of phosphatidylinositol 3-kinase survival pathway
Authors: Mao Weike , Iwai Chikao , Keng Peter C. , Vulapalli Raju , Liang Chang-seng
Published: December 2005

Norepinephrine (NE) induces endoplasmic reticulum (ER) unfolded protein response and reduces maturation and translocation of NE transporter to cell membrane via enhanced formation of reactive oxygen species in PC-12 cells. In the present study, we investigated whether ER stress is also implicated in the proapoptotic effect of NE. We found that the apoptotic effect of NE was associated with increased processing of ER-resident pro-caspase-12, cleavage of caspase-9 and -3, and mitochondrial release of cytochrome c. ER stress was evidenced by upregulation of ER chaperone GRP78 and transcription factor CHOP and the translocation of XBP-1 from the ER to the nucleus by NE. NE also reduced phospho-Akt (Ser473), indicating suppression of the phosphatidylinositol 3-kinase (PI3-kinase)/Akt survival pathway. Similar results were produced by thapsigargin. NGF, which promotes the PI3-kinase/Akt activity, reduced the effects of NE and thapsigargin on apoptosis and activation of caspase-12 and -3. However, the effects of NE, but not of thapsigargin, were abolished by pretreatment with SOD and catalase. In contrast, the PI3-kinase inhibitors LY-294002 and wortmannin abolished the protective effects of both SOD/catalase and NGF on NE-induced apoptosis. The functional importance of caspase-12 activation was supported by the use of Z-ATAD-FMK, which reduced the NE-induced processing of caspase-12 and cell apoptosis, but the caspase-12, -9, and -3 inhibitors had no effects on the increase in cytosolic cytochrome c produced by NE. In contrast, the release of mitochondrial cytochrome c was abolished by SOD/catalase and NGF. These results indicate that NE induced cell apoptosis by both ER stress and a mitochondrial death pathway and that the effects of NE were mediated via oxidative stress and inhibition of the PI3-kinase/Akt survival pathway.
Different metabolic responses to central and peripheral injection of enterostatin
Authors: Lin Ling , Park MieJung , Hulver Matt , York David A.
Published: December 2005

Enterostatin, a pentapeptide cleaved from procolipase, suppresses fat intake after peripheral and central administration. Chronic treatment of rats with enterostatin decreases body weight and body fat. The effect was greater than could be accounted by the reduction in food intake alone. Hence, we have investigated the effect of enterostatin on energy metabolism. Male Sprague-Dawley rats adapted to a high-fat diet were implanted with lateral cerebral ventricular or amygdala cannulas. The metabolic effects were determined by indirect calorimetry. After habituation to the test cages, fasted rats were injected with either saline vehicle or enterostatin given either intraperitoneally (100 nmol) or intracerebroventricularly (1 nmol) or into specific brain regions [amygdala (0.01 nmol) or paraventricular nucleus (PVN) (0.1 nmol)]. Respiratory quotient (RQ) and energy expenditure were monitored over 2 h. Intraperitoneal enterostatin reduced RQ (saline: 0.81 ± 0.02 vs. enterostatin: 0.76 ± 0.01) and increased energy expenditure by 44%. Intracerebroventricular enterostatin increased the energy expenditure without any effects on RQ, whereas PVN enterostatin increased metabolic rate, while preventing the increase in RQ observed in the control animals. In contrast, neither RQ nor energy expenditure was altered after enterostatin was injected into the amygdala. Enterostatin activated AMP-activated protein kinase in primary cultures of human myocytes in a dose- and time-dependent manner and increased the rate of fatty acid β-oxidation. These findings suggest that enterostatin regulates energy expenditure and substrate partitioning through both peripheral and central effects.
Vasopressin induces depolarization and state-dependent firing patterns in rat thalamic paraventricular nucleus neurons in vitro
Authors: Zhang L. , Doroshenko P. , Cao X. Y. , Irfan N. , Coderre E. , Kolaj M. , Renaud L. P.
Published: December 2005

The thalamic midline paraventricular nucleus (PVT) is prominently innervated by vasopressin-immunoreactive neurons from the suprachiasmatic nucleus (SCN), site of the brain's biological clock. Using patch-clamp recordings in slice preparations taken from Wistar rats during the subjective day, we examined 90 PVT neurons for responses to bath-applied AVP (0.5–2 μM; 1–3 min). In current clamp at resting membrane potentials (−65 ± 1 mV), PVT neurons displayed low-threshold spikes (LTSs) and burst firing patterns. In 50% of cells tested, AVP induced a slowly rising, prolonged membrane depolarization and tonic firing, returning to burst firing upon recovery. AVP modulated hyperpolarization-activated LTSs by decreasing the time to the initial sodium spike at the onset of LTS, also increasing the duration of the afterdepolarization. Responses were blockable with a V1a receptor antagonist (Manning compound). Under voltage clamp, AVP induced a TTX-resistant, slowly rising, and prolonged (∼15 min) inward current (<40 pA). Current-voltage relationship ( I-V) analyses of the AVP responses revealed a decrease in membrane conductance to 73.1 ± 6.2% of control, with net AVP current reversing at −106 ± 4 mV, and decreased inward rectification at negative potentials. These observations are consistent with an AVP-induced closure of an inwardly rectifying potassium conductance. On the basis of these in vitro observations, we suggest that the SCN vasopressinergic innervation of PVT is excitatory in nature, possibly releasing AVP with circadian rhythmicity and contributing to state-dependent firing patterns in PVT neurons over the sleep-wake cycle.
Comparable GABAergic Mechanisms of Hippocampal Seizurelike Activity in Posttetanic and Low-Mg2+ Conditions
Authors: Fujiwara-Tsukamoto Yoko , Isomura Yoshikazu , Takada Masahiko
Published: December 2005

It is known that GABA is a major inhibitory neurotransmitter in mature mammalian brains, but the effect of this substance is sometimes converted into depolarizing or even excitatory when the postsynaptic Cl– concentration becomes high. Recently we have shown that seizurelike afterdischarge induced by tetanic stimulation in normal extracellular fluid (posttetanic afterdischarge) is mediated through GABAergic excitation in mature hippocampal CA1 pyramidal cells. In this study, we examined the possible contribution of similar depolarizing/excitatory GABAergic input to the CA1 pyramidal cells to the seizurelike afterdischarge induced in a low extracellular Mg2+ condition, another experimental model of epileptic seizure activity (low-Mg2+ afterdischarge). Perfusion of the GABAA antagonist bicuculline abolished the low-Mg2+ afterdischarge, but not the interictal-like activity, in most cases. Each oscillatory response during the low-Mg2+ afterdischarge was dependent on Cl– conductance and contained an F–-insensitive depolarizing component in the pyramidal cells, thus indicating that the afterdischarge response may be mediated through both GABAergic and nonGABAergic transmissions. In addition, local GABA application to the recorded cells revealed that GABA responses were indeed depolarizing during the low-Mg2+ afterdischarge. Furthermore, the GABAergic interneurons located in the strata pyramidale and oriens fired in oscillatory cycles more actively than those in other layers of the CA1 region. These results suggest that the depolarizing GABAergic input may facilitate oscillatory synchronization among the hippocampal CA1 pyramidal cells during the low-Mg2+ afterdischarge in a manner similar to the expression of the posttetanic afterdischarge.
Morphine Directly Inhibits Nociceptors in Inflamed Skin
Authors: Wenk Heather N. , Brederson Jill-Desiree , Honda Christopher N.
Published: December 2005

Peripherally delivered opiates attenuate mechanical and thermal hyperalgesia in experimental models of inflammation, suggesting that activation of peripheral opioid receptors decreases the excitability of nociceptors in inflamed tissues. The current study examines the effects of peripheral morphine sulfate on response properties of sensory neurons in healthy and inflamed skin. Afferent units (185) were isolated from tibial nerve of rats using an in vitro glabrous skin-nerve teased-fiber preparation. Of these, 107 units were from normal healthy skin, and 78 were from inflamed skin 18 h after intraplantar injection of complete Freund's adjuvant. As a population, C-fiber units innervating inflamed skin exhibited properties characteristic of sensitization when compared with units innervating healthy control skin. Mechanical thresholds were lowered, responses to noxious mechanical and thermal stimuli were elevated, a greater proportion of units was spontaneously active, and the average rate of spontaneous discharge was higher. Response properties in other conduction velocity groups remained unchanged. Fifty-eight percent of C and C/Aδ nociceptors innervating inflamed skin were opiate-sensitive, and their excitability was attenuated by direct application of morphine to their receptive fields. All morphine-sensitive units were nociceptors from inflamed skin with conduction velocities <1.3 m/s. Morphine effects were concentration-dependent and naloxone-sensitive, indicating that the effects were receptor-mediated. These findings provide direct evidence that morphine acts through peripheral opioid receptors to inhibit the activity of cutaneous nociceptors under conditions of inflammation.
Temporal Nonlinearity During Recovery From Sequential Inhibition by Neurons in the Cat Primary Auditory Cortex
Authors: Nakamoto Kyle T. , Zhang Jiping , Kitzes Leonard M.
Published: December 2005

Auditory stimuli occur most often in sequences rather than in isolation. It is therefore necessary to understand how responses to sounds occurring in sequences differ from responses to isolated sounds. Cells in primary auditory cortex (AI) respond to a large set of binaural stimuli when presented in isolation. The set of responses to such stimuli presented at one frequency comprises a level response area. A preceding binaural stimulus can reduce the size and magnitude of level response areas of AI cells. The present study focuses on the effects of the time interval between a preceding stimulus and the stimuli of a level response area in pentobarbital-anesthetized cats. After the offset of a preceding stimulus, the ability of AI cells to respond to succeeding stimuli varies dynamically in time. At short interstimulus intervals (ISI), a preceding stimulus can completely inhibit responses to succeeding stimuli. With increasing ISIs, AI cells respond first to binaural stimuli that evoke the largest responses in the control condition, i.e., not preceded by a stimulus. Recovery rate is nonlinear across the level response area; responses to these most-effective stimuli recover to 70% of control on average 187 ms before responses to other stimuli recover to 70% of their control sizes. During the tens to hundreds of milliseconds that a level response area is reduced in size and magnitude, the selectivity of AI cells is increased for stimuli that evoke the largest responses. This increased selectivity results from a temporal nonlinearity in the recovery of the level response area which protects responses to the most effective binaural stimuli. Thus in a sequence of effective stimuli, a given cell will respond selectively to only those stimuli that evoke a strong response when presented alone.
Endogenous Acetylcholine Enhances Synchronized Interneuron Activity in Rat Neocortex
Authors: Bandyopadhyay Susanta , Sutor Bernd , Hablitz John J.
Published: December 2005

Application of 4-aminopyridine (4-AP) along with EAA) receptor antagonists produces γ-aminobutyric acid (GABAA) receptor-dependent synchronized activity in interneurons. This results in waves of activity propagating through upper cortical layers. Because interneurons in the neocortex are excited by nicotinic acetylcholine receptor (nAChR) agonists, ACh may influence synchronization of these local neocortical interneuronal networks. To study this possibility, we have used voltage-sensitive dye imaging using the fluorescent dye RH 414 (30 μM) in rat neocortical slices. Recordings were obtained in the presence of 4-AP (100 μM) and the EAA receptor antagonists d-2-amino-5-phosphonvaleric acid (20 μM) and 6-cyano-7-nitro-quinoxaline-2,3-dione (10 μM). In response to intracortical stimulation, localized or propagated activity restricted to upper cortical layers was seen. Bath application of the ACh esterase inhibitor neostigmine (10 μM) and the nAChR agonist 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP; 10 μM) increased the response amplitude, the extent of spread, and the duration of this activity. These changes were seen in 13 of 16 slices tested with neostigmine (10 μM) and 4 of 7 slices tested with DMPP (10 μM). Application of the muscarinic AChR antagonist atropine (1 μM) did not block the enhancement of activity by neostigmine ( n = 7). Application of dihydro-β-erythroidine (10 μM), known, at this concentration, to selectively antagonize α4β2-like nAChRs, blocked the effect of neostigmine ( n = 5). The selective α7-like nAChR antagonist methyllycaconitine (50 nM) was ineffective ( n = 5). These results suggest that activation of α4β2-like nAChRs by endogenously released ACh can enhance synchronized activity in local neocortical inhibitory networks.
Spatial Integration of Optic Flow Signals in Fly Motion-Sensitive Neurons
Authors: Neri Peter
Published: December 2005

Neurons in the fly lobula plate integrate motion signals over large regions of visual space in a directionally selective manner. This study is concerned with the details of this integration process. We used a stimulus consisting of a 4 × 4 lattice of locally moving Gabor patches, in which each patch could take any direction independently. We also presented only one patch at a time or two patches at a time. Across all possible directions of motion, the firing rate response r1+2 to two simultaneously presented patches was well described by r1+2(d1, d2) = G × [r1(d1) + r2(d2)] + S, where r1 and r2 are responses to individual patches moving in directions d1 and d2, and G ∼ 0.81, S ∼ −23. However, this quasi-linear scaling expression failed to account for three main empirical observations: 1) the directional-tuning curve for one patch is broader in the presence of another patch moving in the neuron’s preferred direction (PD); 2) the vertical compression of this curve is greater when the second patch moves in the antipreferred direction (AD) as opposed to PD; 3) the ability of the neuronal response to discriminate the direction of a patch is greater when the other patch is moving in the PD as opposed to AD, where this ability is assessed using both information theory and a standard discriminability index. To account for these departures from the simple scaling model, we used a normalization model very similar to one used for macaque area MT/V5. This model can qualitatively explain all three departures from the scaling equation described above, suggesting that a gain-control normalization network may be at work within the fly lobula plate.
Encoding Changes in Orbitofrontal Cortex in Reversal-Impaired Aged Rats
Authors: Schoenbaum Geoffrey , Setlow Barry , Saddoris Michael P. , Gallagher Michela
Published: December 2005

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.
Serotonin Modulates the Properties of Ascending Commissural Interneurons in the Neonatal Mouse Spinal Cord
Authors: Zhong Guisheng , Díaz-Ríos Manuel , Harris-Warrick Ronald M.
Published: December 2005

The interneuron populations that constitute the central pattern generator (CPG) for locomotion in the mammalian spinal cord are not well understood. We studied the properties of a set of commissural interneurons whose axons cross and ascend in the contralateral cord (aCINs) in the neonatal mouse. During N-methyl-d-aspartate (NMDA) and 5-HT–induced fictive locomotion, a majority of lumbar (L2) aCINs examined were rhythmically active; most of them fired in phase with the ipsilateral motoneuron pool, but some fired in phase with contralateral motoneurons. 5-HT plays a critical role in enabling the locomotor CPG to function. We found that 5-HT increased the excitability of aCINs by depolarizing the membrane potential, reducing the postspike afterhyperpolarization amplitude, broadening the action potential, and decreasing the action potential threshold. Serotonin had no significant effect on the input resistance and sag amplitude of aCINs. These results support the hypothesis that aCINs play important roles in coordinating left–right movements during fictive locomotion and thus may be component neurons in the locomotor CPG in neonatal mice.
Consumer attitudes towards female nudity in advertising: An empirical study
Authors: Beetles Andrea C. , Harris Lloyd C.
Published: December 2005

Female nudity in advertising varies greatly across Europe and the world. However, in studying extant literature regarding female nudity in advertising a number of limitations emerge. In particular, existing research into consumer attitudes fails to recognize sexuality and cultural differences. The aim of this research is to explore and describe consumer attitudes to the depiction of female nudity in advertising in the UK; a previously overlooked context. In addition, in order to overcome omissions in existing empirical research, a secondary aim is to explore such issues from a variety of perspectives by noting and incorporating into the analysis participant sexuality. The literature review concentrates on the key areas of sex roles in advertising, sex appeal and arousal in advertising, female nudity in advertising and the application of literary, feminist and art theory to advertising research. Thereafter follows a discussion and justification of focus groups as the chosen method that incorporates a detailed description of the informants (including details of informant sexuality and sex) as well as a breakdown of the choice of advertising material. Following from this are the results and discussion that focus on six key themes: sex and sex approval; the gaze; sexual and non-sexual use of nudity; femininity and androgyny; congruence; and authorial intent and reader response. The article concludes with a discussion of the main implications of the study and with the forwarding of suggestions for further research.
Productive Play
Authors: Pearce Celia
Published: December 2005

In this article, the author argues against the assertion, originating with “canonical” game studies texts such as Homo Ludens and Man, Play, and Games, that inherent in the definition of games is that they are “unproductive.” Instead, she makes a case for the notion of productive play, in which creative production for its own sake (as opposed to production for hire) is an active and integral part of play activities, particularly those enabled by networks. Citing from her recent ethnographic research studying intergame immigration between massively multiplayer online games (MMOGs), the author describes one case in which players ejected from the MMOGUru: Ages Beyond Myst became highly productive, creating artifacts from Uru in other virtual worlds like There and Second Life. Over time, the Uru Diaspora expanded the game's culture, eventually creating their own original Uru-and Myst-inspired artifacts, including an entirely new game.
A Ludicrous Discipline? Ethnography and Game Studies
Authors: Boellstorff Tom
Published: December 2005

The information age has, under our noses, become the gaming age. It appears likely that gaming and its associated notion of play may become a master metaphor for a range of human social relations, with the potential for new freedoms and new creativity as well as new oppressions and inequality. Although no methodological or theoretical approach can represent a cure-all for any discipline, in this article the author discusses how anthropological approaches can contribute significantly to a game studies nimble enough to respond to the unanticipated, conjunctural, and above all rapidly changing cyberworlds through which everyone in some way is now in the process of redefining the human project.