bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular signal transduction pathways induced by leptin in C2C12 cells
Authors: Maroni Paola , Bendinelli Paola , Piccoletti Roberta
Published: June 2005

As experimental evidence suggests that leptin may have direct effects on peripheral tissues, we investigated some of the transductional molecules induced by leptin in C2C12 cells. In immunoprecipitation experiments using anti‐p85 antibodies (a regulatory subunit of phosphatidylinositol‐3‐kinase; PI3K), we observed a significant increase in PI3K activity. Immunoblot analyses showed that Akt, GSK3, ERK1, ERK2, and p38 mitogen‐activated protein kinase (p38 MAPK) phosphorylation significantly increased after leptin treatment. Protein kinase C (PKC)‐ζ was also activated by leptin, as documented by an immunocomplex kinase assay and immunoblotting experiments. The treatment of C2C12 cells with Wortmannin before leptin administration inhibited induction of the phosphorylation of ERKs (extracellular signal‐regulated kinases) but not that of p38 MAPK, whereas pre‐treatment with a PKC‐ζ inhibitor partially decreased ERK phosphorylation. Taken together, our in vitro results further support the hypothesis that leptin acts acutely on skeletal muscle tissue through some of the components of insulin signalling, including PKC‐ζ.
Oligomycin strengthens the effect of cyclosporin A on mitochondrial permeability transition by inducing phosphate uptake
Authors: Chávez Edmundo , Rodríguez José S. , García Gerardo , García Noemí , Correa Francisco
Published: June 2005

The purpose of this work was to assess the effect of oligomycin on the mitochondrial membrane permeability transition. The antibiotic was found to strengthen cyclosporin A (CSA)‐induced protection of non‐specific permeability, which is triggered by a matrix Ca2+ load in the absence of ADP. Oligomycin also reinforced the protective effect of CSA on carboxyatractyloside‐induced pore opening in the absence of ADP, but failed to do so in mitochondria incubated under anaerobic conditions or after addition of CCCP. Analyzing the efflux of matrix Ca2+, we found that mitochondrial swelling and the collapse of the transmembrane electric gradient coincided with membrane leakage. The effects of the antibiotic were observed in phosphate‐containing media but not in the presence of acetate. Furthermore, N‐ethylmaleimide hindered the protective effect of oligomycin—CSA. In addition, the matrix phosphate concentration increased concurrently with a diminution in the matrix‐free fraction of Ca2+. We concluded that oligomycin increases phosphate uptake by stimulating the phosphate−/OH− exchange reaction.
Characterization of ATP and ADP hydrolysis activity in rat gastric mucosa
Authors: Savegnago Lucielli , Nogueira Cristina W. , Fachinetto Roselei , Rocha Joao Batista Teixeira
Published: June 2005

The degradation of nucleotides is catalyzed by the family of enzymes called nucleoside triphosphate diphosphohydrolases (NTPDases). The aim of this work was to demonstrate the presence of NTPDase in the rat gastric mucosa. The enzyme was found to hydrolyze ATP and ADP at an optimum pH of 8.0 in the presence of Mg2+ and Ca2+. The inhibitors ouabain (0.01–1 mM), N‐ethylmaleimide (0.01–4 mM), levamisole (0.10–0.2 mM) and Ap5A (0.03 mM) had no effect on NTPDase 1 activity. Sodium azide (0.03–30 mM), at high concentrations (>0.1 mM), caused a parallel hydrolysis inhibition of ATP and ADP. Suramin (50–300 μM) inhibited ATP and ADP hydrolysis at all concentrations tested. Orthovanadate slightly inhibited (15%) Mg2+and Ca2+ ATP/ADPase at 100 μM. Lanthanum decreased Mg2+ and Ca2+ ATP/ADPase activities. The presence of NTPDase as ecto‐enzyme in the gastric mucosa may have an important role in the extracellular metabolism of nucleotides, suggesting that this enzyme plays a role in the control of acid and pepsin secretion, mucus production, and contractility of the stomach.
Osteocalcin is angiogenic in vivo
Authors: Cantatore Francesco Paolo , Crivellato Enrico , Nico Beatrice , Ribatti Domenico
Published: June 2005

The exact function of osteocalcin (OC), a protein synthesized by osteoblasts during the matrix mineralization phase, is still unknown. In this study we investigated the capacity of OC to promote vasoproliferation in chick embryo chorioallantoic membrane (CAM), a well established in vivo assay for angiogenesis and anti‐angiogenesis. The results showed that OC stimulates angiogenesis and that the response is similar to that obtained with FGF‐2, a well‐known angiogenic cytokine. It has previously been demonstrated that OC is involved in bone repair, so the angiogenic activity reported here might also play a crucial role in bone formation.
Computed tomography guided lumbar sympathetic block for complex regional pain syndrome in a child: A case report and review
Authors: Nordmann Giles R. , Lauder Gillian R. , Grier David J.
Published: June 2005

The aim of this paper is to describe the first reported use of computed tomography (CT) guided lumbar sympathetic block as treatment of a case of complex regional pain syndrome (CRPS) in a child. The potential aetiology of CRPS is discussed in relation to the mechanism of action of local anaesthetics used in the block. Based on the successful treatment of this child and the documented success of its use in adults, we conclude that despite the minimal dose of radiation given, CT guided lumbar sympathetic block is an important treatment option in CRPS in children.
Nucleotide binding to the homodimeric MJ0796 protein: A computational study of a prokaryotic ABC transporter NBD dimer
Authors: Campbell Jeff D. , Sansom Mark S.P.
Published: June 2005

Transport by ABC proteins requires a cycle of ATP‐driven conformational changes of the nucleotide binding domains (NBDs). We compare three molecular dynamics simulations of dimeric MJ0796: with ATP was present at both NBDs; with ATP at one NBD but ADP at the other; and without any bound ATP. In the simulation with ATP present at both NBDs, the dimeric protein interacts with the nucleotides in a symmetrical manner. However, if ADP is present at one binding site then both NBD–NBD and protein–ATP interactions are enhanced at the opposite site.
Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions
Authors: Knerr Ina , Schubert Steffen W. , Wich Christina , Amann Kerstin , Aigner Thomas , Vogler Tina , Jung Ronny , Dötsch Jörg , Rascher Wolfgang , Hashemolhosseini Said
Published: June 2005

Glial cells missing a (GCMa) belongs to a new transcription factor family. Syncytin was shown to be a target gene of GCMa. Here, we demonstrate that the protein kinase A (PKA) pathway acts upstream of GCMa. After transient transfection of BeWo cells with PKA, GCMa transcriptional activity and both GCMa and syncytin transcripts were upregulated. This increase was accompanied by further cellular differentiation. Using normoxic or hypoxic conditions to mimic pathophysiological settings known to diminish trophoblast differentiation, we found that gene repressive effects of oxygen deficiency were compensated by the induction of the PKA pathway. We propose that GCMa‐driven syncytin expression is the key mechanism for syncytiotrophoblast formation.
Broad-bandwidth, sound scattering, and absorption from krill (Meganyctiphanes norvegica), mysids (Praunus flexuosus and Neomysis integer), and shrimp (Crangon crangon)
Authors: Conti Stéphane G. , Demer David A. , Brierley Andrew S.
Published: June 2005

Sound scattering and absorption by Northern krill (Meganyctiphanes norvegica) were measured over the acoustic bandwidth of 30–210 kHz and compared with similar scattering measurements for Antarctic krill (Euphausia superba). The measurements of total target strength (TTS; energy scattered in all directions, averaged over all angles of incidence) match the SDWBA model (stochastic distorted-wave Born approximation) recently developed for Antarctic krill, indicating its validity for other euphausiid species with similar size and shape. However, the TTS of crustaceans with markedly different shapes are not well predicted by SDWBA derived with the generic krill shape and scaled to animal length (L). Therefore, crustacean target strength (TS) may not be estimated accurately by a linear function of log10(L), irrespective of shape, questioning the validity of the current TS relationship used for Antarctic krill derived from data measured from multiple crustaceans. TTS and TS are dependent upon both L and shape, and different crustaceans have significantly different shapes and width-to-length relationships. In contrast, modelled TTS and TS spectra for gravid and non-gravid krill appear to have differing amplitudes, but similar shapes. Additionally, measurements of absorption spectra from decapods indicate that the absorption cross-section increases with the volume of the animal.
Did over-reliance on commercial catch rate data precipitate the collapse of northern cod?
Authors: Shelton Peter A.
Published: June 2005

It has been suggested that a number of “lessons” can be learned from the collapse of the northern cod stock off Newfoundland and Labrador. However, not all purported lessons have been validated with available data. One lesson is thought to be that over-reliance on commercial catch rate data and an incorrect assumption regarding the functional relationship between catch rate and population size were major contributors to overestimating stock size, precipitating the collapse. The current study describes calibration approaches used in assessments, and evaluates alternative functional relationships between commercial catch rates and stock size. In addition, historical population size is re-estimated using only research vessel data and compared with estimates obtained based on both commercial catch rate and research vessel data. Calibration with commercial catch rate contributed to overestimating stock size in some years, but there is no evidence that the assumed functional relationship between commercial catch rate and population size was a significant factor in the collapse.
QuickBird‐based analysis for the spatial characterization of archaeological sites: Case study of the Monte Serico medieval village
Authors: Lasaponara Rosa , Masini Nicola
Published: June 2005

The potential of high‐resolution QuickBird satellite imagery for archaeological investigations is assessed in the well documented site of Monteserico Village in the Southern Italy. The considered test site presents complex topographical and morphological features, typical of many medieval settlements, which make archaeological prospection with any remote sensing technologies difficult. Results from our investigations showed that the QuickBird fused products can be a valuable data source for reconstructing the urban shape of buried settlements up to single building scale.
Heterogeneous dynamics of poly(vinyl acetate) far above Tg: A combined study by dielectric spectroscopy and quasielastic neutron scattering
Authors: Tyagi Madhusudan , Alegría Angel , Colmenero Juan
Published: June 2005

We have investigated the dynamics of poly(vinly acetate) using broadband dielectric spectroscopy (DS) covering over 14 decades in frequency up to 20GHz and high-resolution quasielastic neutron-scattering (QENS) technique. The dielectric results have been interpreted in terms of the phenomenological Kohlrausch–Williams–Watts [G. Williams and D. C. Watts, Trans. Faraday Soc. 66, 80 (1970); F. Alvarez, A. Alegría, and J. Colmenero, Phys. Rev. B 47, 125 (1993)] description. Because of the wide frequency range covered by DS, it provides a precise determination of dynamics over a wide temperature range and it revealed a crossover in polymer dynamics at 387K through different dielectric parameters, viz., characteristic times, asymmetric shape parameter, and dielectric strength. Moreover, shape parameter is found to be higher in comparison to other typical polymeric systems. The characteristic relaxation times observed by QENS displayed an anomalous dependence of momentum transfer, indicating the possible existence of heterogeneities in the system even at the high temperatures. In addition, spin-lattice relaxation times, T1, were found to be decoupled from dielectric characteristic times. Based on these results, a model was proposed to account for heterogeneities where we consider coexistence of different regions with standard polymeric behavior but with different characteristic times, leading to a distribution of relaxation times. The model is found to account for the anomalous behavior and an inherent shape parameter is found to account for the shape of α relaxation. This model is also found to predict the T variation of T1 characteristic time scales at all temperatures. The origin of the heterogeneous domains is believed to lie in the microstructure of polymer chains.
Seiberg-Witten equations in R4: Lie symmetries, particular solutions, integrability
Authors: Aleynikov Dmitriy V.
Published: June 2005

It is shown that the 11-parameter automorphism group of Lie algebra of four-dimensional Euclidean group is a maximal Lie symmetries group of the Seiberg-Witten equations in R4. Particular explicit solutions which are invariant under SO(3) subgroups of the maximal Lie symmetries group are constructed. It is established that Seiberg-Witten equations do not possess the Painlevé property. Nevertheless, SO(3) invariant solutions obtained are turned to admit a characteristic singularity structure.
Exchange spring media for perpendicular recording
Authors: Suess D. , Schrefl T. , Fähler S. , Kirschner M. , Hrkac G. , Dorfbauer F. , Fidler J.
Published: June 2005

A novel type of exchange spring media is proposed for magnetic recording systems consisting of a hard/soft bilayer. Finite element micromagnetic simulations show that the reversal modes induced by the external write field are significantly different from the thermally activated switching processes. Thus, the bilayers can be optimized in order to achieve a high thermal stability without increase of coercive field. In grains with identical size and coercivity an optimized bilayer reaches an energy barrier exceeding those of optimized single phase media by more than a factor of two. Additionally the lower angular dependence of coercivity of exchange spring media will improve the signal to noise ratio.
Organic-inorganic hybrid photopolymer with reduced volume shrinkage
Authors: Kim Won Sun , Jeong Yong-Cheol , Park Jung-Ki
Published: June 2005

An organic-inorganic hybrid photopolymer containing surface-photoreactive nanoparticles, which exhibits a significant enhancement in optical properties is reported. The photopolymer containing surface-photoreactive nanoparticles showed high diffraction efficiency near 90% and reduced volume shrinkage without affecting the energetic sensitivity and optical quality of the photopolymer.
High-performance polymer light-emitting diodes utilizing modified Al cathode
Authors: Guo Tzung-Fang , Yang Fuh-Shun , Tsai Zen-Jay , Wen Ten-Chin , Hsieh Sung-Nien , Fu Yaw-Shyan
Published: June 2005

We report an increase of electroluminescence (EL) efficiency by two orders of magnitude for poly(2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene) (MEH-PPV) based polymer light-emitting diodes (PLED) while employing Al as the cathode with an ultrathin layer of poly(ethylene oxide) (PEO). EL efficiencies of MEH-PPV PLEDs biased at 10 mA were found to be 0.017cd∕A at 31cd∕m2, 1.50cd∕A at 2515cd∕m2, and 4.96cd∕A at 8416cd∕m2 for applying Al, PEO∕Al, and PEO∕LiF∕Al as the device cathodes, respectively. The significant improvement in the device performance is attributed to the promotion of minority carrier injection (electrons), where the threshold of the injection can be characterized through the deviation of Fowler–Nordhiem tunneling prediction.
Pressure-dependent Schottky barrier at the metal-nanotube contact
Authors: Park Noejung , Kang Donghoon , Hong Suklyun , Han Seungwu
Published: June 2005

We carry out first-principles density-functional calculations to investigate the electronic structure of the gold-carbon nanotube contact. It is found that a pressure applied on the gold-nanotube contact shifts the Fermi level from the valence edge to the conduction edge of the carbon nanotube. This can explain the n-type transport behavior frequently observed in the nanotube field-effect transistor using the gold as electrodes. An atomistic model is proposed for a possible origin of the pressure when the nanotube is embedded in the gold electrode.
Carrier dynamics in Ga0.53In0.47As∕InP near-surface quantum wells
Authors: Symonds Clémentine , Mangeney Juliette , Saint-Girons Guillaume , Sagnes Isabelle
Published: June 2005

Ga 0.53 In 0.47 As ∕ InP single-quantum wells with thin top barrier layers of InP and InAlAs have been studied by pump-probe experiments and temperature-dependent photoluminescence spectroscopy. The carrier lifetimes are shorter in samples with an InAlAs surface barrier than with an InP surface barrier. The decays consist in an early stage decay of typically 30 ps and an extended stage decay of several hundreds of picoseconds. This nonexponential relaxation is the result of thermally activated carrier escape, trapping, and recombination on the surface states. Two nonradiative surface states, at 11 and 68 meV from the ground state of the quantum well, were identified.
A tumor necrosis factor receptor family protein serves as a cellular receptor for the macrophage-tropic equine lentivirus
Authors: Zhang Baoshan , Jin Sha , Jin Jing , Li Feng , Montelaro Ronald C.
Published: June 2005

Characterization of cellular receptors for human, simian, and feline immunodeficiency viruses that are tropic for lymphocytes and macrophages have revealed a common theme of a sequential binding of viral envelope proteins with two coreceptors to mediate virus infection of target cells. In contrast to these dual tropic immunodeficiency viruses, the ungulate lentiviruses, including equine infectious anemia virus (EIAV), exclusively infect cells of the monocyte-macrophage lineage to cause progressive degenerative diseases without clinical immunodeficiency. EIAV causes a uniquely dynamic disease that is characterized by recurrent disease episodes including fever, diarrhea, lethargy, anemia, and thrombocytopenia. Although EIAV provides an important animal model for lentivirus disease resulting from macrophage infection, to date there has been no definition of the specific cellular receptor(s) used by the equine lentivirus to infect target cells. In the current study, we have identified and cloned a functional receptor for EIAV, designated equine lentivirus receptor-1 (ELR1), related to the family of TNF receptor (TNFR) proteins. ELR1 was shown to be expressed in various equine cells permissive for EIAV replication
in vitro
, including monocytes and macrophages. In contrast, EIAV-resistant human, murine, and simian cells were negative for ELR1 expression but became susceptible to virus infection when transduced with a recombinant murine retrovirus expressing the ELR1. Thus, these results identify a specific functional receptor for a macrophagetropic lentivirus and indicate that infection by EIAV may be mediated by a single receptor, in contrast to coreceptors used by the lymphotropic immunodeficiency lentiviruses.
The application of statistical physics to evolutionary biology
Authors: Sella Guy , Hirsh Aaron E.
Published: June 2005

A number of fundamental mathematical models of the evolutionary process exhibit dynamics that can be difficult to understand analytically. Here we show that a precise mathematical analogy can be drawn between certain evolutionary and thermodynamic systems, allowing application of the powerful machinery of statistical physics to analysis of a family of evolutionary models. Analytical results that follow directly from this approach include the steady-state distribution of fixed genotypes and the load in finite populations. The analogy with statistical physics also reveals that, contrary to a basic tenet of the nearly neutral theory of molecular evolution, the frequencies of adaptive and deleterious substitutions at steady state are equal. Finally, just as the free energy function quantitatively characterizes the balance between energy and entropy, a free fitness function provides an analytical expression for the balance between natural selection and stochastic drift.
Drug resistance in cancer: Principles of emergence and prevention
Authors: Komarova Natalia L. , Wodarz Dominik
Published: June 2005

Although targeted therapy is yielding promising results in the treatment of specific cancers, drug resistance poses a problem. We develop a mathematical framework that can be used to study the principles underlying the emergence and prevention of resistance in cancers treated with targeted small-molecule drugs. We consider a stochastic dynamical system based on measurable parameters, such as the turnover rate of tumor cells and the rate at which resistant mutants are generated. We find that resistance arises mainly before the start of treatment and, for cancers with high turnover rates, combination therapy is less likely to yield an advantage over single-drug therapy. We apply the mathematical framework to chronic myeloid leukemia. Early-stage chronic myeloid leukemia was the first case to be treated successfully with a targeted drug, imatinib (Novartis, Basel). This drug specifically inhibits the BCR-ABL oncogene, which is required for progression. Although drug resistance prevents successful treatment at later stages of the disease, our calculations suggest that, within the model assumptions, a combination of three targeted drugs with different specificities might overcome the problem of resistance.
Functional antagonism between
Helicobacter pylori
CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells
Authors: Yokoyama Kazuyuki , Higashi Hideaki , Ishikawa Susumu , Fujii Yumiko , Kondo Satoshi , Kato Hiroyuki , Azuma Takeshi , Wada Akihiro , Hirayama Toshiya , Aburatani Hiroyuki , Hatakeyama Masanori
Published: June 2005

Chronic infection with
cagA
-positive
Helicobacter pylori
is associated with the development of atrophic gastritis, peptic ulcers, and gastric adenocarcinoma. The
cagA
gene product CagA is injected into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Translocated CagA disturbs cellular functions by physically interacting with and deregulating intracellular signaling transducers through both tyrosine phosphorylation-dependent and -independent mechanisms. To gain further insights into the pathophysiological activities of CagA in gastric epithelial cells, we executed a genome-wide screening of CagA-responsive genes by using DNA microarray and identified nuclear factor of activated T cells (NFAT) transcription factors whose binding sites were overrepresented in the promoter regions of CagA-activated genes. Results of reporter assays confirmed that CagA was capable of activating NFAT in a manner independent of CagA phosphorylation. Expression of CagA in gastric epithelial cells provoked translocation of NFATc3, a member of the NFAT family, from the cytoplasm to the nucleus and activated an NFAT-regulated gene,

p21
WAF1/Cip1

. CagA-mediated NFAT activation was abolished by inhibiting calcineurin or phospholipase Cγ activity. Furthermore, treatment of cells with
H. pylori
VacA (vacuolating toxin), which inhibits NFAT activity in T lymphocytes, counteracted the ability of CagA to activate NFAT in gastric epithelial cells. These findings indicate that the two major
H. pylori
virulence factors inversely control NFAT activity. Considering the pleiotropic roles of NFAT in cell growth and differentiation, deregulation of NFAT, either positively or negatively, depending on the relative exposure of cells to CagA and VacA, may contribute to the various disease outcomes caused by
H. pylori
infection.
Scaling and memory in volatility return intervals in financial markets
Authors: Yamasaki Kazuko , Muchnik Lev , Havlin Shlomo , Bunde Armin , Stanley H. Eugene
Published: June 2005

For both stock and currency markets, we study the return intervals τ between the daily volatilities of the price changes that are above a certain threshold
q
. We find that the distribution function

P
q

(τ) scales with the mean return interval

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\begin{equation*}{\bar {{\tau}}}\end{equation*}\end{document}

as

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\begin{equation*}P_{q}({\tau})={\bar {{\tau}}}^{-1}f({\tau}/{\bar {{\tau}}})\end{equation*}\end{document}

. The scaling function
f
(
x
) is similar in form for all seven stocks and for all seven currency databases analyzed, and
f
(
x
) is consistent with a power-law form,
f
(
x
) ∼
x
-γ
with γ ≈ 2. We also quantify how the conditional distribution

P
q

(τ|τ
0
) depends on the previous return interval τ
0
and find that small (or large) return intervals are more likely to be followed by small (or large) return intervals. This “clustering” of the volatility return intervals is a previously unrecognized phenomenon that we relate to the long-term correlations known to be present in the volatility.
Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors
Authors: Sankaran Sumathi , Guadalupe Moraima , Reay Elizabeth , George Michael D. , Flamm Jason , Prindiville Thomas , Dandekar Satya
Published: June 2005

Limited information is available on the molecular mechanisms by which long-term HIV-1-infected nonprogressors suppress HIV-1 infection and maintain immune functions. The intestinal mucosal immune system is an early target for HIV-1 infection and severe CD4
+
T cell depletion. We evaluated mucosal T lymphocyte subsets, virus-specific cellular responses, gene expression profiles, and viral loads in intestinal mucosal biopsies of long-term nonprogressor (LTNP) patients as compared to chronically HIV-1-infected patients with high viral loads (HVLs) and CD4
+
T cell loss, as well as HIV-seronegative healthy individuals. This study aims to identify the mucosal correlates of HIV disease progression and to determine the molecular changes associated with immune and intestinal dysfunction. LTNP patients had undetectable viral loads, normal CD4
+
T cell levels, and virus-specific cellular responses in peripheral blood and mucosal compartments. Microarray analysis revealed a significant increase in gene expression regulating immune activation, cell trafficking, and inflammatory response in intestinal mucosa of HVL patients as compared to LTNP patients. Genes associated with cell cycle regulation, lipid metabolism, and epithelial cell barrier and digestive functions were down-regulated in both HVL and LTNP patients. This may adversely influence nutrient adsorption and digestive functions, with the potential to impact the efficacy of antiretroviral therapy. We demonstrate that the maintenance of mucosal T cells, virus-specific responses, and distinct gene expression profiles correlate with clinical outcome in LTNP patients. However, the intestinal mucosal immune system remains an important target of HIV-1 infection in LTNP, and these effects may ultimately contribute toward disease progression.
Ras activity regulates cyclin E degradation by the Fbw7 pathway
Authors: Minella Alex C. , Welcker Markus , Clurman Bruce E.
Published: June 2005

The Skp1–Cullin1 F-box protein–Fbw7 ubiquitin ligase regulates phosphorylation-dependent cyclin E degradation, and disruption of this pathway is associated with genetic instability and tumorigenesis. Fbw7 is a human tumor suppressor that is targeted for mutation in primary cancers. However, mechanisms other than mutation of Fbw7 may also disrupt cyclin E proteolysis in cancers. We show that oncogenic Ha-Ras activity regulates cyclin E degradation by the Fbw7 pathway. Activated Ras impairs Fbw7-driven cyclin E degradation, and, conversely, inhibition of normal Ras activity decreases cyclin E abundance. Moreover, activation of the mitogen-activated protein kinase pathway is the essential Ras function that inhibits cyclin E turnover, and activated Ha-Ras expression inhibits both the binding of cyclin E to Fbw7 and cyclin E ubiquitination. Last, we found that oncogenic Ras activity potentiates cyclin E-induced genetic instability but only when cyclin E is susceptible to degradation by Fbw7. Thus, we conclude that Ras activity regulates Fbw7-mediated cyclin E proteolysis and suggest that impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis.
Central memory self/tumor-reactive CD8
+
T cells confer superior antitumor immunity compared with effector memory T cells
Authors: Klebanoff Christopher A. , Gattinoni Luca , Torabi-Parizi Parizad , Kerstann Keith , Cardones Adela R. , Finkelstein Steven E. , Palmer Douglas C. , Antony Paul A. , Hwang Sam T. , Rosenberg Steven A. , Waldmann Thomas A. , Restifo Nicholas P.
Published: June 2005

Central memory CD8
+
T cells (T
CM
) and effector memory CD8
+
T cells (T
EM
) are found in humans and mice; however, their relative contributions to host immunity have only recently been examined
in vivo
. Further, the ability of T
CM
to treat an established tumor or infection has yet to be evaluated. To address the therapeutic potential of different tumor-reactive CD8
+
T cell memory subsets, we used an established model for the
in vitro
generation of T
CM
and T
EM
by using IL-15 and IL-2, respectively. Adoptively transferred T
CM
exhibited a potent
in vivo
recall response when combined with tumor-antigen vaccination and exogenous IL-2, leading to the eradication of large established tumors. By contrast, T
EM
were far less effective on a per-cell basis. Microarray analysis revealed that the signature of highly
in vivo
effective antitumor T cells included the overexpression of genes responsible for trafficking to secondary lymphoid tissues. This gene expression profile correctly predicted the
in vitro
and
in vivo
lymphoid-homing attributes of tumor-reactive T cells. Furthermore, we found that homing to secondary lymphoid tissue is required for optimal tumor treatment. Our findings indicated that highly
in vivo
effective antitumor T cells were those that initially targeted secondary lymphoid tissue, rather than tumor sites, as had previously been postulated. Thus, tumor-reactive CD8
+
T cell populations with the phenotypic and functional attributes of T
CM
may be superior to T
EM
/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination.
Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis
Authors: Tang Qi-Qun , Grønborg Mads , Huang Haiyan , Kim Jae-Woo , Otto Tamara C. , Pandey Akhilesh , Lane M. Daniel
Published: June 2005

CCAAT enhancer-binding protein (C/EBP)β, C/EBPα, and peroxisome proliferator activated receptor (PPAR)γ act in a cascade where C/EBPβ activates expression of C/EBPα and PPARγ, which then function as pleiotropic activators of genes that produce the adipocyte phenotype. When growth-arrested 3T3-L1 preadipocytes are induced to differentiate, C/EBPβ is rapidly expressed but still lacks DNA-binding activity. After a long (14-hour) lag, glycogen synthase kinase 3β enters the nucleus, which correlates with hyperphosphorylation of C/EBPβ and acquisition of DNA-binding activity. Concurrently, 3T3-L1 preadipocytes synchronously enter S phase and undergo mitotic clonal expansion, a prerequisite for terminal differentiation.
Ex vivo
and
in vitro
experiments with C/EBPβ show that phosphorylation of Thr-188 by mitogen-activating protein kinase “primes” C/EBPβ for subsequent phosphorylation on Ser-184 and Thr-179 by glycogen synthase kinase 3β, acquisition of DNA-binding function, and transactivation of the C/EBPα and PPARγ genes. The delayed transactivation of the C/EBPα and PPARγ genes by C/EBPβ appears necessary to allow mitotic clonal expansion, which would otherwise be prevented, because C/EBPα and PPARγ are antimitotic.
Increasing the power of functional maps of the medial temporal lobe by using large deformation diffeomorphic metric mapping
Authors: Miller Michael I. , Beg M. Faisal , Ceritoglu Can , Stark Craig
Published: June 2005

The functional magnetic resonance imagery responses of declarative memory tasks in the medial temporal lobe (MTL) are examined by using large deformation diffeomorphic metric mapping (LDDMM) to remove anatomical variations across subjects. LDDMM is used to map the structures of the MTL in multiple subjects into extrinsic atlas coordinates; these same diffeomorphic mappings are used to transfer the corresponding functional data activation to the same extrinsic coordinates. The statistical power in the averaged LDDMM mapped signals is significantly increased over conventional Talairach–Tournoux averaging. Activation patterns are highly localized within the MTL. Whereas the present demonstration has been aimed at enhancing alignment within the MTL, this technique is general and can be applied throughout the brain.
A database analysis method identifies an endogenous trans-acting short-interfering RNA that targets the
Arabidopsis ARF2, ARF3
, and
ARF4
genes
Authors: Williams Leor , Carles Cristel C. , Osmont Karen S. , Fletcher Jennifer C.
Published: June 2005

Two classes of small RNAs, microRNAs and short-interfering RNA (siRNAs), have been extensively studied in plants and animals. In
Arabidopsis
, the capacity to uncover previously uncharacterized small RNAs by means of conventional strategies seems to be reaching its limits. To discover new plant small RNAs, we developed a protocol to mine an
Arabidopsis
nonannotated, noncoding EST database. Using this approach, we identified an endogenous small RNA, trans-acting short-interfering RNA–auxin response factor (tasiR-ARF), that shares a 21- and 22-nt region of sequence similarity with members of the
ARF
gene family. tasiR-ARF has characteristics of both short-interfering RNA and microRNA, recently defined as tasiRNA. Accumulation of trans-acting siRNA depends on DICER-LIKE1 and RNA-DEPENDENT RNA POLYMERASE6 but not RNA-DEPENDENT RNA POLYMERASE2. We demonstrate that tasiR-ARF targets three
ARF
genes,
ARF2, ARF3
/
ETT
, and
ARF4
, and that both the tasiR-ARF precursor and its target genes are evolutionarily conserved. The identification of tasiRNA-ARF as a low-abundance, previously uncharacterized small RNA species proves our method to be a useful tool to uncover additional small regulatory RNAs.
Initial synthesis and structure of an all-ferrous analogue of the fully reduced [Fe
4
S
4
]
0
cluster of the nitrogenase iron protein
Authors: Scott Thomas A. , Berlinguette Curtis P. , Holm Richard H. , Zhou Hong-Cai
Published: June 2005

The synthetic cubane-type iron–sulfur clusters [Fe
4
S
4
(SR)
4
]

z

form a four-member electron transfer series (
z
= 3–, 2–, 1–, and 0), all members of which except that with
z
= 0 have been isolated and characterized. They serve as accurate analogues of protein-bound [Fe
4
S
4
(SCys)
4
]

z

redox centers, which, in terms of core oxidation states, exhibit the redox couples [Fe
4
S
4
]
3+/2+
and [Fe
4
S
4
]
2+/1+
. Clusters with the all-ferrous core [Fe
4
S
4
]
0
have never been isolated because of their oxidative sensitivity. Recent work on the Fe protein of
Azotobacter vinelandii
nitrogenase has demonstrated the formation of the all-ferrous state upon reaction with a strong reductant. Treatment of the cyanide cluster [Fe
4
S
4
(CN)
4
]
3–
with K[Ph
2
CO] in acetonitrile/tetrahydrofuran affords the all-ferrous cluster [Fe
4
S
4
(CN)
4
]
4–
, isolated as the Bu
4
N
+
salt. The x-ray structure demonstrates retention of a cubane-type structure with idealized
D
2

d

symmetry. The Mössbauer spectrum unambiguously demonstrates the [Fe
4
S
4
]
0
oxidation state. Bond distances, core volumes,
57
Fe isomer shifts, and visible absorption spectra make evident the high degree of structural and electronic similarity with the fully reduced Fe protein. The attribute of cyanide ligation causes positive [Fe
4
S
4
]
2+/1+
and [Fe
4
S
4
]
1+/0
redox potential shifts, facilitating the initial isolation of an analogue of the [Fe
4
S
4
]
0
protein site.
A secreted regulatory protein couples transcription to the secretory activity of the
Pseudomonas aeruginosa
type III secretion system
Authors: Urbanowski Mark L. , Lykken Guinevere L. , Yahr Timothy L.
Published: June 2005

The type III secretion system (T3SS) of
Pseudomonas aeruginosa
is an important virulence determinant. Transcription of the T3SS is highly regulated and intimately coupled to the activity of the type III secretion channel. The secretion channel is generally closed, and transcription is repressed. Inducing signals such as calcium depletion, however, open the secretion channel and derepress transcription of the T3SS. The coupling of transcription with secretion requires three previously identified cytoplasmic regulatory proteins. ExsA is a DNA-binding protein required for transcriptional activation of the entire T3SS. The second regulatory protein, ExsD, functions as anti-activator by directly binding to ExsA. Finally, ExsC functions as an anti-anti-activator by directly binding to and inhibiting ExsD. Although the regulatory roles of ExsC, ExsD, and ExsA were defined through these previous studies, the mechanism of coupling transcription to secretion was unclear. We now report the identification of ExsE as a secreted regulator of the T3SS and provide evidence that ExsE functions as a direct inhibitor of ExsC. When the secretion channel is closed, ExsE is complexed with ExsC in the cytoplasm, and transcription of the T3SS is repressed by sequestration of ExsA by ExsD. We propose that the secretion of ExsE provides an initiating signal that results in an equilibrium shift whereby ExsC becomes preferentially bound to ExsD, thus allowing liberated ExsA to activate transcription of the T3SS. The presence of ExsE homologs in the T3SSs of other bacterial species suggests that this mechanism of coupling transcription to secretion may be commonly used.
Nutrition education for illiterate children in southern Madagascar – addressing their needs, perceptions and capabilities
Authors: Mahr Johanna , Wuestefeld Marzella , ten Haaf Joep , Krawinkel Michael B
Published: June 2005

Objective

A Knowledge, Attitudes and Practices (KAP) study was conducted in three villages of Bekily District in southern Madagascar prior to the implementation of a health education programme with children. The participatory learning concept of the Child-to-Child approach was followed to involve the children in the planning and implementation of the programme, which was covered by the German Agency for Technical Cooperation.

Design

To this effect, qualitative research methods such as Participatory Learning and Action techniques (focus group discussions, mapping and matrix ranking, etc.) were applied.

Subjects

The survey was conducted between August and December 1999. It involved a total of 55 school-aged children (6–14 years) along with 21 mothers and 34 fathers, representing different ethnic groups and educational backgrounds.

Results

The results show that children's KAP related to health and nutrition strongly reflect those of adults. They are not aware of a possible link between bad hygiene and the occurrence of diseases. According to them, diarrhoea or malaria is caused by consuming too large amounts of certain foods. Even if they know about certain elementary hygiene behaviours, they do not practise this in their everyday life.

Conclusion

A major objective of the health education programme for children should be to tackle the discrepancy between hygiene-related knowledge and behaviour. Through the participatory study approach the children revealed their ability to contribute to the programme development. In using appropriate communication channels, the Child-to-Child health education programme is expected to influence the health behaviours of both adults and children. The health education programme should be combined with a literacy programme to address the children's desire to learn reading and writing.
Complementary foods consumed by 6 – 12-month-old rural infants in South Africa are inadequate in micronutrients
Authors: Faber Mieke
Published: June 2005

Objective

To determine the nutrient composition of complementary foods consumed by 6–12-month-old South African infants.

Design

Nutrient intake was determined for infants who were recruited to participate in a randomised controlled trial using a single 24-hour dietary recall.

Setting/subjects

Infants aged 6–12 months (n = 475) residing in The Valley of a Thousand Hills, a rural area in KwaZulu-Natal, South Africa.

Results

Energy and protein intakes from complementary foods were adequate. Infants who consumed infant products (commercially available fortified infant cereals/ready-to-eat canned baby foods/formula milk powder) had significantly higher intakes of calcium, iron, zinc, vitamin A, thiamine, riboflavin, niacin, vitamin B6, vitamin B12 and vitamin C than infants who did not consume any infant products. For infants who consumed infant cereals (n = 142), these cereals provided 51% of total iron intake. Infant cereals provided more than 25% of total intake for magnesium, thiamine, niacin and vitamin B12. For infants consuming ready-to-eat canned baby foods (n = 77), these products contributed less than 15% of total intake for all the micronutrients. The nutrient density of the complementary diet was less than half the desired density for calcium, iron and zinc. Animal products were consumed by 17% of infants, 26% consumed dairy products and 18% consumed vitamin-A-rich fruit and vegetables during the 24-hour recall period.

Conclusion

The nutrient composition of complementary foods among rural South African infants was inadequate, especially for iron, zinc and calcium. Strategies should be developed to improve the nutritional quality of their diets.
Women's iodine status and its determinants in an iodine-deficient area in the Kayes region, Mali
Authors: Torheim Liv E , Granli Gry I , Sidibé Cheick S , Traoré Abdel K , Oshaug Arne
Published: June 2005

Objective

To assess iodine status and its determinants in women of childbearing age in a rural area in the Kayes region, Mali, West Africa.

Design

Cross-sectional study where women's iodine status was indicated by urinary iodine concentration (UIC) and level of goitre based on palpation. Salt iodine was assessed semi-quantitatively at household level. Individual characteristics were collected using questionnaires.

Setting

Fifteen villages in a rural area in the Kayes region of Mali.

Subjects

Women aged 15–45 years (n = 423).

Results

Median UIC was 2.7 μg dl−1, and only 6% of the women had adequate iodine status of UIC > 10 μg dl−1. Most women (60%) had visible goitre, and only 9% were classified as without goitre. Only 39% of the households were using salt with any iodine, and level of knowledge about salt iodisation was low. Main determinants of UIC were breast-feeding and level of salt iodisation; currently breast-feeding women had lower UIC, and UIC increased with increasing level of iodine in household salt. Prevalence of goitre was lower in older women with higher body mass index.

Conclusion

The study indicates severe iodine deficiency in the study area. Urgent action is needed to improve the situation through enforcing salt iodisation legislation and increasing the level of knowledge about the importance of iodised salt in the population.
Nutrition and the burden of disease in New Zealand: 1997–2011
Authors: Stefanogiannis Niki , Lawes Carlene MM , Turley Maria , Tobias Martin , Vander Hoorn Stephen , Mhurchu Cliona Ni , Rodgers Anthony
Published: June 2005

Objective

To estimate the burden of disease due to selected nutrition-related risk factors (high total blood cholesterol, high systolic blood pressure, high body mass index (BMI) and inadequate vegetable and fruit intake) in 1997, as well as the burden that could potentially be avoided in 2011 if small, favourable changes in the current risk factor distribution were to occur.

Design

Data on risk factor levels, disease burden and risk associations were combined using comparative risk assessment methodology, a systematic approach to estimating both attributable and avoidable burden of disease. Disease outcomes assessed varied according to risk factor and included ischaemic heart disease, stroke, type 2 diabetes mellitus and selected cancers.

Setting

New Zealand.

Results

Approximately 4500 deaths (17% of all deaths) in 1997 were attributable to high cholesterol, 3500 (13%) to high blood pressure, 3000 (11%) to high BMI and 1500 (6%) to inadequate vegetable and fruit intake. Taking prevalence overlap into account, these risk factors were estimated jointly to contribute to approximately 11 000 (40%) deaths annually in New Zealand. Approximately 300 deaths due to each risk factor could potentially be avoided in 2011 if modest changes were made to each risk factor distribution.

Conclusions

High cholesterol, blood pressure and BMI, as well as inadequate vegetable and fruit intake, are major modifiable causes of death in New Zealand. Small changes in the population distribution of these risk factors could have a major impact on population health within a decade.
Comparison between household budget survey and 24-hour recall data in a nationally representative sample of Polish households
Authors: Sekula W , Nelson M , Figurska K , Oltarzewski M , Weisell R , Szponar L
Published: June 2005

Objective

Household budget survey (HBS) data are used regularly for nutritional epidemiological purposes. The validity of HBS data, however, is not well established. The aim of this project was to compare HBS and individual nutrition survey (INS) data in a nationally representative sample of Polish households.

Design

Estimates of food consumption and nutrient intake were compared between household food acquisition data collected over 1 month and a single 24-hour recall collected from every household member in a nationally representative sample of Polish households surveyed between September and November 2000. To facilitate the comparison, INS food consumption data excluded food eaten away from home and were modified using a computer program to estimate food ‘as purchased’ (including disaggregation of recipe data) and to allow for wastage.

Setting

Poland.

Subjects

Participants were 3716 individuals in 1215 households (representing co-operation rates of 86.2% and 89.2%, respectively).

Results

Good agreement was shown between median estimates of foods such as potatoes, vegetables (including processed), meat, meat products and poultry, and animal fats (excluding butter), but agreement was poor for bread and rolls, fruit, vegetable fats and oils, eggs and six other food groups. Estimates of energy and nutrient intake were within ±10% with the exceptions of polyunsaturated fats, potassium and vitamin C.

Conclusions

Possible reasons for differences in findings between the two surveys include survey bias (e.g. social approval bias leading to overreporting of fruit), seasonal variations (e.g. high potato purchases between September and November) and aspects of the methodology (e.g. HBS data were based on records collected over 1 month, whereas 24-hour recall data were based on recalls collected from all household respondents on only 1 day and averaged for each household type). HBSs provide useful data for epidemiological research, but findings need to be interpreted in the light of other data regarding consumption, and numerous factors that may affect consumption need to be taken into account.