bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian Rhythms in the Mouse: A Connections Map
Authors: Van Gelder Russell N.
Published: September 2003

Genetic and biochemical experiments over the past decade have facilitated the construction of a viable working model for the molecular mechanisms that generate the circadian rhythm in
Mus musculus
. The basic mechanism consists of two intertwined transcription-translation negative feedback loops. One, the "positive loop," controls the rhythmic expression of a Per-Arnt-Sim (PAS)-domain-containing positive transcription factor, BMAL1 (also called MOP3). The other, the "negative loop," controls the transcription of
mPeriod
1 and 2 and
mCryptochrome
1 and 2, two families of genes that encode repressor proteins. The loops are intertwined because the proteins mPeriod and mCryptochrome directly repress transcription mediated by the CLOCK:BMAL1 heterodimer, whereas CLOCK:BMAL1 drives transcription of the
mPeriod
and
mCryptochrome
genes, as well as that of
Rev-erb-alpha
, a repressor of
Bmal1
expression. Mutations, including the tau mutation in hamsters [encoding Casein kinase I ϵ (CkIϵ)], have identified essential functions for other proteins in the timekeeping mechanism. The master pacemaker for circadian rhythms in mice is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light cycles can synchronize molecular rhythms in the SCN by stimulating the release of glutamate and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) from melanopsin-containing retinal ganglion cells. This results in increased transcription of
mPeriod
genes and a shift in the phase of the clock. This Pathway Map of the murine circadian mechanism describes the individual known components of the mouse circadian clock and their mutual interactions.

Science Viewpoint

R. N. Van Gelder, E. D. Herzog, W. J. Schwartz, P. H. Taghert, Circadian rhythms: In the loop at last.
Science
300
, 1534-1535 (2003). [
Abstract
] [
Full Text
]
Synaptic Vesicle Fusion Followed by Clathrin-Mediated Endocytosis
Authors: Galli Thierry , Haucke Volker , Gough Nancy R.
Published: September 2003

The animation shows calcium-stimulated exocytosis of synaptic vesicles followed by clathrin-mediated vesicle recycling. Many of the molecular components that are involved in synaptic vesicle priming, docking, fusion, and endocytosis are shown. Although the process in the animation describes synaptic vesicle cycling, similar cellular processes occur for most calcium-coupled secretory and clathrin-mediated endocytotic events. The animation could be used to help illustrate the sequence of events associated with both exocytosis and endocytosis, as well as aid in understanding the processes involved in neurotransmitter release in response to nerve stimulation.

[
Resource Details
]
Wnt Signaling Pathways Mediated by Ca
2+
and Cyclic GMP
Authors: Wang Hsien-yu , Malbon Craig C.
Published: September 2003

Wnts are secreted glycoprotein ligands that bind to and signal through Frizzleds, which are receptors of the seven-transmembrane, heterotrimeric guanine nucleotide-binding protein (G protein) -coupled receptor family. Wnt-Frizzled signaling is critical in a wide spectrum of developmental roles including cell fate, polarity, differentiation, migration, and proliferation. The Wnt family in mammals includes nearly 20 members and some, such as Wnt-4, -5A, and -11, activate Frizzleds that do not normally lead to the stabilization of intracellular concentrations of β-catenin, but instead operate largely in a β-catenin-independent manner. Studies (first in
Xenopus
and zebrafish, and later in mammalian cells) demonstrated that activation of Frizzled-2 by Wnt-5A stimulated the phosphatidylinositol pathway and an increase in intracellular Ca
2+
concentration. Characterization of the proximal signaling revealed that Wnt-5A activates Frizzled-2, G proteins, and the G protein effector phospholipase Cβ (PLCβ), stimulating an accumulation of intracellular inositol trisphosphate (IP
3
) and diacylglycerol (DAG). Elevation of IP
3
leads to intracellular Ca
2+
release and subsequent activation of Ca
2+
-calmodulin-dependent protein kinase II, as well as the calcium-sensitive protein phosphatase calcineurin. Elevation of intracellular DAG activates protein kinase C (PKC). These pathways allow Wnt-5A to regulate the activity of transcription factors that control those genes activated in response to Wnt-5A. The G protein G
t2
(known also as transducin2) and its effector, guanosine 3′,5′-monophosphate (cyclic GMP) phosphodiesterase, are activated also by the Wnt-Frizzled-2 pathway. The sharp decline in intracellular cyclic GMP, which can be blocked by selective cyclic GMP phosphodiesterase inhibitors, is required for Wnt-5A stimulation of primitive endoderm formation in mouse totipotent teratocarcinoma cells and Wnt-5A stimulation of early development in zebrafish embryos.

Science Viewpoint

H.-y. Wang, C. C. Malbon, Wnt signaling, Ca
2+
, and cyclic GMP: Visualizing Frizzled functions.
Science
300
, 1529-1530 (2003). [
Abstract
] [
Full Text
]
Erbin: Sorting Out ErbB2 Receptors or Giving Ras a Break?
Authors: Kolch Walter
Published: September 2003

Erbin is a member of the leucine-rich repeat and PDZ domain (LAP) family. Originally cloned as an epidermal growth factor receptor (EGFR)-associated protein involved in receptor sorting and cell polarization, erbin has now been shown to inhibit EGF signaling by preventing the activation of the Raf-1 kinase by Ras. This discovery provides new insights into the rapidly expanding roles of adaptor and scaffolding proteins in the regulation of receptor signaling. It also highlights the complexity of cellular signaling networks in which the tasks of individual components are determined by the specific functional context.
Mortality in workers in poultry slaughtering/processing plants: the Missouri poultry cohort study: Table 1
Authors: Netto G F , Johnson E S
Published: September 2003

Background:Subjects who work in poultry slaughtering and processing plants have one of the highest human exposures to viruses that cause cancer in chickens and turkeys. It is not known whether these viruses cause cancer in humans also. Epidemiological studies investigating this issue are scarce.

Aims and Methods:Mortality was studied during the period 1969–90 in a cohort of 7700 subjects who worked in poultry slaughtering and processing plants and were members of a local poultry union in the State of Missouri.

Results and Conclusions:Statistically significant excess risks of non-malignant respiratory diseases, accidents, and symptoms, senility, and ill-defined conditions, and increased but not statistically significant excesses for some cancers were observed in particular race/sex groups. Most of these results were based on small numbers of deaths, and in many cases were evident only in particular subgroups of the cohort. Because of this and the multiple comparisons made, chance could not be ruled out in explaining the findings. Furthermore, the cohort is young, with only 6% deceased at the end of follow up. Further follow up of this cohort is required before a reliable assessment of the potential risk associated with these viruses can be made.
Long-Term Inhibition of Rho-Kinase Suppresses Angiotensin II–Induced Cardiovascular Hypertrophy in Rats In Vivo
Authors: Higashi Midoriko , Shimokawa Hiroaki , Hattori Tsuyoshi , Hiroki Junko , Mukai Yasushi , Morikawa Keiko , Ichiki Toshihiro , Takahashi Shosuke , Takeshita Akira
Published: September 2003

Intracellular signaling pathway mediated by small GTPase Rho and its effector Rho-kinase plays an important role in regulation of vascular smooth muscle contraction and other cellular functions. We have recently demonstrated that Rho-kinase is substantially involved in angiotensin II–induced gene expressions and various cellular responses in vitro. However, it remains to be examined whether Rho-kinase is involved in the angiotensin II–induced cardiovascular hypertrophy in vivo and, if so, what mechanisms are involved. Long-term infusion of angiotensin II for 4 weeks caused hypertrophic changes of vascular smooth muscle and cardiomyocytes in rats. Both changes were significantly suppressed by concomitant oral treatment with fasudil, which is metabolized to a specific Rho-kinase inhibitor, hydroxyfasudil, after oral administration. Angiotensin II caused a perivascular accumulation of macrophages and Rho-kinase activation, both of which were also significantly suppressed by fasudil. Vascular NAD(P)H oxidase expression (nox1, nox4, gp91phox, and p22phox) and endothelial production of superoxide anions were markedly increased by angiotensin II, both of which were also significantly suppressed by fasudil. Thus, fasudil ameliorated the impaired endothelium-dependent relaxations caused by angiotensin II without affecting vasodilator function of vascular smooth muscle. These results provide evidence that Rho-kinase is substantially involved in the angiotensin II–induced cardiovascular hypertrophy in rats in vivo. The suppression of endothelial NAD(P)H oxidase upregulation and resultant superoxide production and the amelioration of endothelial vasodilator function may be involved in this process.
International Law, the Crime of Aggression and the Ius Ad Bellum
Authors: Griffiths
Published: September 2003

No Abstract
Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression
Authors: Chen Taoyong , Guo Jun , Yang Mingjin , Han Chaofeng , Zhang Minghui , Chen Wei , Liu Qiuyan , Wang Jianli , Cao Xuetao
Published: September 2003

Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow–derived DCs toward macrophage inflammatory protein-3β (MIP-3β) and induces them to retain responsiveness to MIP-1α after lipopolysaccharide (LPS)–stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor–κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.
Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis
Authors: Joy Anna M. , Beaudry Christian E. , Tran Nhan L. , Ponce Francisco A. , Holz David R. , Demuth Tim , Berens Michael E.
Published: September 2003

Glioma cells that migrate out of the main tumor mass into normal brain tissue contribute to the failure of most gliomas to respond to treatment. Treatments that target migratory glioma cells may enhance the therapeutic response. Multiple lines of evidence suggest that suppression of apoptosis accompanies activation of the migratory phenotype. Here, we determine whether migration and apoptosis are consistently linked in glioma cells and whether manipulation of migration influences cytotoxic therapy-induced apoptosis. Camptothecin and Trail-induced apoptosis were decreased 2-5-fold in actively migrating glioma cells relative to migration-restricted cells. Consistent with a mechanistic link between migration and apoptosis, the dose-response for stimulation of migration on laminin was inversely proportional to apoptosis induction. Treatment of glioma cells with migration inhibitors alone had little effect on basal rates of apoptosis and had little effect on Trail-induced or camptothecin-induced apoptosis in migration-restricted cells. By contrast, migration inhibitors increased camptothecin and Trail-induced apoptosis in actively migrating glioma cells. Migrating glioma cells have increased amounts of phosphorylated Akt and its downstream substrate glycogen synthase kinase-3 relative to migration restricted cells. Treatment of migrating cells with a specific inhibitor of phosphoinositide 3-kinase (PI3-K), LY294002, blocked the phosphorylation of Akt and increased the sensitivity to apoptosis. LY294002 had no effect on the migration of restricted cells. This suggests that migrating glioma cells activate the PI3-K survival pathway, protecting migrating cells from apoptosis. Taken together, these data provide support for a link between migration and apoptosis in glioma cells. In addition, evidence indicates that treatment with migration inhibitors, while not affecting apoptosis-induction in migration-restricted cells, can sensitize migrating glioma cells to cytotoxic agents.
Recombinant bacteria for mosquito control
Authors: Federici B. A. , Park H.-W. , Bideshi D. K. , Wirth M. C. , Johnson J. J.
Published: September 2003

Bacterial insecticides have been used for the control of nuisance and vector mosquitoes for more than two decades. Nevertheless, due primarily to their high cost and often only moderate efficacy, these insecticides remain of limited use in tropical countries where mosquito-borne diseases are prevalent. Recently, however, recombinant DNA techniques have been used to improve bacterial insecticide efficacy by markedly increasing the synthesis of mosquitocidal proteins and by enabling new endotoxin combinations from different bacteria to be produced within single strains. These new strains combine mosquitocidal Cry and Cyt proteins of Bacillus thuringiensiswith the binary toxin of Bacillus sphaericus, improving efficacy against Culex species by 10-fold and greatly reducing the potential for resistance through the presence of Cyt1A. Moreover, although intensive use of B. sphaericus against Culex populations in the field can result in high levels of resistance, most of this can be suppressed by combining this bacterial species with Cyt1A; the latter enables the binary toxin of this species to enter midgut epithelial cells via the microvillar membrane in the absence of a midgut receptor. The availability of these novel strains and newly discovered mosquitocidal proteins, such as the Mtx toxins of B. sphaericus, offers the potential for constructing a range of recombinant bacterial insecticides for more effective control of the mosquito vectors of filariasis, Dengue fever and malaria.
Immobilization of biologically active species on PA‐6 foils treated by a dielectric barrier discharge
Authors: Dumitrascu N. , Borcia G. , Apetroaei N. , Popa G.
Published: September 2003

In the field of biomaterials and biomedical devices, surface activation has been focused on creating functional groups capable of preferential adsorption of biologically active species (proteins, enzymes, cells, drugs, etc.). In this way an interface can be created between the synthetic material and the biological medium, with the aim of increasing the compatibility of the implant with the human organism. In our experiments a dielectric barrier discharge (DBD), in helium at atmospheric pressure, was used as the source of energy capable of creating active centers that render the functionalized surface favorable to immobilization of biological molecules. Retention of immunoglobulin (IgG) and heparin biomolecules on polyamide‐6 (PA‐6) surfaces after treatment by the DBD was analyzed by atomic force microscopy, adhesion evaluation, and measurement of the contact angle titration in order to assess this incorporation on the treated surfaces. The marked adsorption of the biomolecules on the active sites created by DBD on the exposed surfaces also was related to a complex set of processes, such as enhanced roughness, increased surface wettability, and modified distribution of cationic and anionic groups on the treated surfaces. All these factors could promote interfacial interactions between the specific groups of the biomolecules existing in the biological medium and the type of cationic and/or anionic groups present on the surface. The efficiency of the DBD treatment showed that the DBD technique is useful for preactivation of the polymer surface for immobilization of other biologically active species (such as drugs and enzymes). © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1985–1990, 2003
Water absorbency of poly(sodium acrylate) superabsorbents crosslinked with modified poly(ethylene glycol)s
Authors: Zhang Jian , Sun Min‐Wei , Zhang Le , Xie Xu‐Ming
Published: September 2003

A series of novel crosslinkers, polyethylene glycol diacrylate (PEGDA) with different molecular weights, were prepared, consisting of acryloyl end groups and the PEG backbones. The corresponding poly(sodium acrylate) superabsorbents of 60 mol % neutralization degree were synthesized by using ammonium persulfate and dimethylaminoethyl methacrylate as redox initiators in aqueous solution. PEGDA was characterized by FTIR and 1H‐NMR. The maximum of water absorbency (Q) of superabsorbents occurred at a specific mole fraction of crosslinker; Q‐values increased with increasing molecular weight of PEGDA at the same mole fraction, whereas the water absorption rate was the opposite, in which Q‐values decreased gradually with time (>24 h). Compared with superabsorbents containing methylene bisacrylamide crosslinker with PEGDA, the Q‐value of the former was significantly less than that of the latter, although levels of the residual monomer and the soluble polymer were opposite. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1851–1856, 2003
Mechanical and thermal flow properties of wood flour–biodegradable polymer composites
Authors: Lee Seung‐Hwan , Ohkita Tsutomu
Published: September 2003

Wood flour (WF)–polycaprolactone (PCL) and polybutylenesuccinate–butylenecarbonate (PBSC) composites were prepared by knead processing. The effects of a compatibilizer on the tensile and thermal flow properties of the composites were investigated. PCL‐graft‐maleic anhydride (PCL‐g‐MA) was used as a compatibilizer. Tensile properties were improved by adding PCL‐g‐MA to both composites. The tensile strength and Young's modulus were increased from 13 to 27 MPa and 581 to 1011 MPa in WF–PCL (50/50, w/w) composites, respectively, and from 17 to 28 MPa and 814 to 1007 Mpa in WF–PBSC (50/50, w/w) composites, respectively, with the addition of 5% PCL‐g‐MA. Elongation at break increased from 4 to 7% and from 3 to 6% in the WF–PCL and the WF–PBSC composites, respectively. Tensile strength was further increased with increasing WF content in the presence of PCL‐g‐MA. Thermal flow temperature and melt viscosity of the composites were increased, and water absorption and thickness swelling were improved with the addition of PCL‐g‐MA. It was found from the burial test that all composites were more than 40% degraded within 6 weeks, and there was no considerable difference in degradation between composites with PCL‐g‐MA and those without. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1900–1905, 2003
Synthesis and FTIR spectroscopic studies on shear induced oriented liquid crystalline chitin/poly(acrylic acid) composite
Authors: Nge Thi Thi , Hori Naruhito , Takemura Akio , Ono Hirokuni , Kimura Tsunehisa
Published: September 2003

Liquid crystalline chitin/poly(acrylic acid) composite, with its unique optical properties, was fabricated by the free‐radical photopolymerization of acrylic acid in an aligned mesophase. Alignment of the mesophase was achieved by unidirectional shearing. The developed composites, coated on calcium fluoride (CaF2) substrate, were transparent, and the alignment was retained depending on the mesophase composition of the ternary dispersion (chitin microfibrils, water, acrylic acid). According to studies from polarized FTIR spectroscopy, both the degree of orientation and the molecular interactions were strongly affected by respective mesophase behavior. The average molecular chains of chitin microfibrils were oriented along the shear direction. A high dichroic ratio value of about 25, observed in composites of chitin/poly(acrylic acid) with a w/w ratio of 55:45, opens an interesting avenue to prepare a new chitin‐based optically anisotropic composite. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1932–1940, 2003
Predictive factors for malignancy in intraductal papillary–mucinous tumours of the pancreas
Authors: Sugiyama M , Izumisato Y , Abe N , Masaki T , Mori T , Atomi Y
Published: September 2003

Background

Preoperative assessment of the likelihood of malignancy in intraductal papillary–mucinous tumour (IPMT) of the pancreas is often difficult. Predictive factors for malignancy and invasive carcinoma in IPMT were analysed.

Methods

Sixty-two patients with IPMT underwent surgical treatment, with histological confirmation of adenoma in 28, carcinoma in situ in 14 and invasive carcinoma in 20. Tumours were of the main duct type in 14 patients, branch duct type in 32, and combined type in 16. A multivariate analysis of 17 potential predictive factors, including preoperative clinical and imaging findings, was conducted.

Results

Multivariate analysis identified two independent predictive factors for malignancy: mural nodules and main pancreatic duct diameter of 7 mm or more. Mural nodules in the main duct or combined type, and mural nodules and tumour diameter of 30 mm or more in the branch duct type were particularly indicative of malignancy. Mural nodules, jaundice and main duct or combined type were predictors of invasive carcinoma in the multivariate analysis.

Conclusion

The above factors should be considered in the diagnosis of IPMT to facilitate appropriate management.
Familial clustering of abdominal aortic aneurysm—smoke signals, but no culprit genes
Authors: Powell J T
Published: September 2003

Even after 20 years of work
Three streams of visual information processing in V2 of Cebus monkey
Authors: Nascimento‐Silva Sheila , Gattass Ricardo , Fiorani Mario , Sousa Aglai P.B.
Published: September 2003

Gattass and collaborators (Gattass R, Rosa MGP, Souza APB, Piñon MCG, Neuenschwander S [1990a] Braz J Med Biol Res 23:375–393) proposed that the dorsal stream of visual processing, as defined by Ungerleider and Mishkin (Ungerleider LG, Mishkin M [1982] In: Ingle DJ, Goodale MA, Mansfield RJW, editors. Analysis of visual behavior. Cambridge: Massachusetts Institute of Technology. p 549–586), can be subdivided into dorsolateral and dorsomedial streams, and suggested that they may be involved in different aspects of the processing of motion and spatial perception, respectively. The goal of the present study was to provide additional evidence for this hypothesis by using cytochrome oxidase immunohistochemistry combined with retrograde tracing techniques. In Old World monkeys, the locations of visual area 4 (V4; ventral stream) and middle temporal area (MT; dorsal stream) projecting neurons in V2 supports the hypothesis that the cytochrome oxidase (CytOx)–rich thin stripes and the CytOx‐poor interstripes are associated with the ventral stream, and that the CytOx‐rich thick stripes belong to the dorsal stream. In this study we describe, in the New World monkey Cebus, the distribution of retrogradely labeled cells in V2 relative to the CytOx compartments after fluorescent tracers were placed in areas V4, MT, and the parietooccipital area (PO). We found PO‐projecting neurons in CytOx‐rich thick stripes and CytOx‐poor interstripes in V2, whereas MT‐projecting neurons appeared almost exclusively in thick stripes. In contrast, V4‐projecting neurons were located mostly in CytOx‐poor interstripes and CytOx‐rich thin stripes. In addition, V4‐ and MT‐projecting neurons were located mainly in supragranular layers, whereas PO‐projecting neurons were located in supragranular and infragranular layers. These results support the hypothesis for the existence of three distinct streams of visual processing: ventral (including V4), dorsolateral (including MT), and dorsomedial (including PO). J. Comp. Neurol. 466:104–118, 2003. © 2003 Wiley‐Liss, Inc.
AMPA receptors mediate acetylcholine release from starburst amacrine cells in the rabbit retina
Authors: Firth Sally I. , Li Wei , Massey Stephen C. , Marshak David W.
Published: September 2003

The light response of starburst amacrine cells is initiated by glutamate released from bipolar cells. To identify the receptors that mediate this response, we used a combination of anatomical and physiological techniques. An in vivo, rabbit eyecup was preloaded with [3H]‐choline, and the [3H]‐acetylcholine (ACh) released into the superfusate was monitored. A photopic, 3 Hz flashing light increased ACh release, and the selective AMPA receptor antagonist, GYKI 53655, blocked this light‐evoked response. Nonselective AMPA/kainate agonists increased the release of ACh, but the specific kainate receptor agonist, SYM 2081, did not increase ACh release. Selective AMPA receptor antagonists, GYKI 53655 or GYKI 52466, also blocked the responses to agonists. We conclude that the predominant excitatory input to starburst amacrine cells is mediated by AMPA receptors. We also labeled lightly fixed rabbit retinas with antisera to choline acetyltransferase (ChAT), AMPA receptor subunits GluR1, GluR2/3, or GluR4, and kainate receptor subunits GluR6/7 and KA2. Labeled puncta were observed in the inner plexiform layer with each of these antisera to glutamate receptors, but only GluR2/3‐IR puncta and GluR4‐IR puncta were found on the ChAT‐IR processes. The same was true of starburst cells injected intracellularly with Neurobiotin, and these AMPA receptor subunits were localized to two populations of puncta. The AMPA receptors are expected to desensitize rapidly, enhancing the sensitivity of starburst amacrine cells to moving or other rapidly changing stimuli. J. Comp. Neurol. 466:80–90, 2003. © 2003 Wiley‐Liss, Inc.
In vivo role of IFN‐γ produced by antigen‐presenting cells in early host defense against intracellular pathogens
Authors: Suzue Kazutomo , Asai Takashi , Takeuchi Tsutomu , Koyasu Shigeo
Published: September 2003

Antigen‐presenting cells (APC), including dendritic cells and macrophages, produce a large amount of interferon (IFN)‐γ, a crucial cytokine for the control of infectious diseases. To elucidate the role of IFN‐γ from APC in vivo, we employed cytokine receptor common γ subunit (γc) and recombination‐activating gene (Rag)‐2 double‐knockout (γc–/–(y)‐Rag‐2–/–) mice, which are severely impaired in IFN‐γ production and are extremely susceptible to infection of intracellular pathogens including Listeria monocytogenes and Toxoplasma gondii. Adoptive transfer of IFN‐γ‐producing APC increased levels of serum IFN‐γ and the resistance to Listeria. Although depletion of NK cells from Rag‐2–/– mice slightly increased the susceptibility to bacterial infection, they are substantially more resistant than γc–/–(y)‐Rag‐2–/– mice, which are also devoid of all lymphoid cells. These results demonstrate that the APC‐derived IFN‐γ contributes to the control of infectious agents in vivo.
The OBF‐1 gene locus confers B cell‐specific transcription by restricting the ubiquitous activity of its promoter
Authors: Massa Steffen , Junker Steffen , Schubart Karin , Matthias Gabriele , Matthias Patrick
Published: September 2003

Transcription of the gene encoding the transcriptional coactivator Oct‐binding factor 1 (OBF‐1)/OCA‐B/Bob.1 is largely restricted to B cells. During B cell development OBF‐1 expression shows two peaks, one in immature B cells in the bone marrow and the other in germinal center B cells. Promoter analysis has identified a cAMP response element (CRE)‐binding site present in the OBF‐1 proximal promoter that is crucial for activity in B cells and for the induction of OBF‐1 expression upon stimulation with CD40 ligand/IL‐4. Here we address the question of how transcription of the OBF‐1 gene is restricted to B cells. Surprisingly, in transient transfection assays the OBF‐1 proximal promoter exhibited an equally strong activity in B and non‐B cells. In contrast, upstream promoter regions displayed B cell‐specific properties, partly overlapping with DNaseI hypersensitive sites identified in this study. In mice, expression of a neomycin resistance gene under the control of a Polyoma enhancer/TK promoter cassette was restricted to B cells when integrated into the OBF‐1 locus, but was ubiquitous when integrated into two other loci, Oct‐1 or the large subunit of RNA polymerase II.Therefore, lineage commitment of the OBF‐1 gene is promoter independent and is achieved by regulating the entire locus in a B cell‐specific manner.
MEF2C regulates c‐Jun but not TNF‐α gene expression in stimulated mast cells
Authors: Wei Xudong , Sun Weiyong , Fan Ruihua , Hahn Joanne , Joetham Anthony , Li Guiming , Webb Saiphone , Garrington Timothy , Dakhama Azzeddine , Lucas Joseph , Johnson Gary L. , Gelfand Erwin W.
Published: September 2003

Mitogen‐activated protein kinase (MAPK) cascades play essential roles in the transduction of extracellular signals to cytoplasmic and nuclear effectors. The MAPK kinase kinase MEKK2 is essential for activation of c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinase 5 (ERK5). These pathways are important for expression of specific cytokine genes in mast cells following cross‐linking of the high‐affinity IgE receptor (FcϵRI). A consequence of ERK5 activation is activation of the transcriptional factor myocyte enhancing factor‐2C (MEF2C), leading to increased c‐Jun expression. We have investigated the role of MEF2C activation in mast cells and demonstrated that it requires sequential activation of the signaling cascade of MEKK2‐MEK5‐ERK5. Following phosphorylation of MEF2C, activated MEF2C regulates transcription of c‐Jun but not TNF‐α. Inhibition of ERK5, MEK5 activation or activation of MEKK2‐deficient mast cells was associated with inhibition of MEF2C phosphorylation and a decrease in c‐Jun expression. Thus, these data define an activation module, MEKK2‐MEK5‐ERK5‐MEF2C in the transcriptional activation of c‐Jun in mast cells following FcϵRI cross‐linking. These results demonstrate the novel and important, MEKK2‐dependent role of MEF2C in induction of c‐Jun expression in mast cells activated through FcϵRI, a pathway distinct from that involving MEKK2‐MEK5‐ERK5 in the regulation of mast cell cytokine production.
The influence of CD95L expression on tumor rejection in mice
Authors: Igney Frederik H. , Behrens Christian K. , Krammer Peter H.
Published: September 2003

Many tumors express the death ligand CD95L (CD178, APO‐1L, FasL) and can kill activated T cells in vitro. This may enable the tumor cells to suppress anti‐tumor immune responses, a phenomenon called "tumor counterattack". Preliminary evidence of tumor counterattack in human tumors exists. However, CD95L‐expressing tumors are rapidly rejected in mice. In order to clarify this controversial situation we investigated whether the level or the time point of CD95L expression might be critical factors determining tumor counterattack versus tumor rejection. We generated CD95‐resistant tumor cell lines expressing different levels of CD95L (LKC‐CD95L). In nude mice the CD95L expression level had no influence on the growth of the CD95L+ tumors. In contrast, a CD95L– control tumor cell line (LKC) grew much faster. In addition, we generated a CD95‐resistant cell line in which CD95L was induced via the tet system (LKCR‐tetCD95L). Induction of CD95Lin established tumors in nude and NOD/SCID mice led to rapid rejection of the tumors. Induction of lower CD95L expression levels delayed tumor rejection only marginally. These results demonstrate that rejection of CD95L‐expressing tumors in mice is not a result of overexpression and does not depend on the presence of CD95L at the onset of tumor progression.
Differential effects of US2, US6 and US11 human cytomegalovirus proteins on HLA class Ia and HLA‐E expression: impact on target susceptibility to NK cell subsets
Authors: Llano Manuel , Gumá Mónica , Ortega Mara , Angulo Ana , López‐Botet Miguel
Published: September 2003

We compared in an inducible expression system the individual effect of US2, US6 and US11 human cytomegalovirus (HCMV) proteins on HLA‐E and HLA class Ia surface expression, assessing in parallel their influence on target susceptibility to NK cell clones. To this end, the RPMI 8866 B lymphoma cell line (HLA‐A2, HLA‐A3, HLA‐B7, HLA‐Cw7, HLA‐ER, HLA‐EG) was stably cotransfected with the ecdysone receptor, together with the US sequences under the control of an ecdysone‐inducible promoter. Biosynthesis of viral proteins was turned on by incubating transfectants with Ponasterone A. US6 down‐regulated expression of all class I molecules, hampering target resistance to NK cell clones controlled by the CD94/NKG2A, KIR2DL2 and/or CD85j (ILT2 or LIR‐1) inhibitory receptors. By contrast, US11 reduced the surface levels of class Ia molecules but preserved HLA‐E; this rendered US11+ cells sensitive to NK clones under the control of KIR2DL2 and/or CD85j, while their resistance to CD94/NKG2A+KIR2DL2– effector cells was maintained. US2 preserved as well HLA‐E expression but selectively targeted class Ia molecules; in fact, HLA‐A and HLA‐C allotypes were down‐modulated whereas HLA‐B7 remained unaltered. US2+ targets became sensitive to KIR2DL2+ cells but remained resistant to CD94/NKG2A+CD85j+ NK clones. The differential effects of US proteins on HLA class Ia and HLA‐E likely reflect the evolutionary adaptation of HCMV to counteract NK‐mediated surveillance.
Study on the development of pomegranate juice processing technology: Clarification of pomegranate juice
Authors: Vardin Hasan , Fenercioǧlu Hasan
Published: September 2003

The effects of clarification agents and methods on pomegranate juice quality were studied. Fruits were pressed as whole, and extracted juice was clarified with gelatin, polyvinylypolypyrrolidone (PVPP) and natural sedimentation. In order to determine the effects of these clarifying techniques on product quality, pH, total phenolic substances (TPS( anthocyanin, turbidity, and total colour density tests were applied to each sample. In clarification, the main purpose was to reduce the amount of phenolic substances. Phenolic substances were controlled in each clarification method. The most effective method was the application of 1 g/L gelatine for clarification. Sensory evaluation also applied for clarified juices and gelatin application was selected by panelists to be superior.
A Direct Synthesis of Nucleoside Analogs Homologated at the 3′‐ and 5′‐Positions
Authors: Schmidt Jürgen , Eschgfäller Bernd , Benner Steven A.
Published: September 2003

A new route is presented to prepare analogs of nucleosides homologated at the 3′‐ and 5′‐positions. This route, applicable to both the D‐ and L‐enantiomeric forms, is suitable for the preparation of monomeric bis‐homonucleosides needed for the synthesis of oligonucleotide analogs. It begins with the known monobenzyl ether 3 of pent‐2‐yne‐1,5‐diol, which is reduced to alkenol 4. Sharpless asymmetric epoxidation of 4, followed by opening of the epoxide 5 with allylmagnesium bromide, gives a mixture of diols 6 and 7. Protection of the primary alcohol as a silyl ether followed by treatment with OsO4, NaIO4, and mild acid in MeOH, followed by reduction, yields (2R,3R) {{[(tert‐butyl)diphenylsilyl]oxy}methyl}tetrahydro‐2‐(2‐hydroxyethyl)‐5‐methoxyfuran (=methyl 3‐{{[(tert‐butyl)diphenylsilyl]oxy}methyl}‐2,3,5‐trideoxy‐α/β‐D‐erythro‐hexafuranoside; 10) (Scheme 1). Protected nucleobases are added to this skeleton with the aid of trimethylsilyl triflate (Scheme 2). The o‐toluoyl (2‐MeC6H4CO) and p‐anisoyl (4‐MeOC6H4CO) groups were used to protect the exocyclic amino group of cytosine. The bis‐homonucleoside analogs 11 and 14a are then converted to monothiol derivatives suitable for coupling (Schemes 3 and 4) to oligonucleotide analogs with bridging S‐atoms. This synthesis replaces a much longer synthesis for analogous nucleoside analogs that begins with diacetoneglucose (=1,2 : 5,6‐di‐O‐isopropylideneglucose), with the stereogenic centers in the final products derived from the Sharpless asymmetric epoxidation. The new route is useful for large‐scale synthesis of these building blocks for the synthesis of oligonucleotide analogs.
Synthesis and Glycosidase Inhibitory Activity of 7‐Deoxycasuarine
Authors: Carmona Ana T. , Whigtman Richard H. , Robina Inmaculada , Vogel Pierre
Published: September 2003

Reaction of 1,4‐anhydro‐2,3,5‐tri‐O‐benzyl‐1‐deoxy‐1‐imino‐D‐arabinitol N‐oxide (8) with allyl alcohol produced a 3.6 : 1 mixture of the two pyrrolo[1,2‐b]isoxazole derivatives 13 and 14. The major adduct 13 was converted to 7‐deoxycasuarine (7), a potent, specific, and competitive inhibitor of amyloglucosidase from Rhizopus mold (see Table).
Maternal distancing and event memory at 20 months
Authors: Prudhomme Nathalie
Published: September 2003

Maternal distancing strategies (Sigel, 1993 in The Development and Meaning of Psychological Distance, Cocking R, Renninger KA (eds). Erlbaum: Hillsdale, NJ; 141–158) with 20‐month‐olds were analysed during a mother–child interaction in a free play situation. Then, they were related to memory performance of the children as assessed by the elicited imitation paradigm with 4 three‐step sequences of actions (Bauer, Hertsgaard, Child Dev. 1993; 64:1204). The aim of this work was to (1) confirm that the Sigel's model of distancing could be used with very young children under two; (2) study relationships between maternal distancing that stimulate representational competence of the child and memory performance of the children. Results showed two different patterns of correlations depending on the sequence type: for enabling sequences, significant positive correlations were obtained for the first two distancing levels whereas for arbitrary sequences no correlation was found whatever the distancing level. As discussed, the first pattern brings new arguments in support of declarative memory before the age of 2 years and reframes the memory development in a Vygotskyian interactionist perspective. The second pattern of correlations calls for replication and more investigation about the processes implied in memory of very young children for different sequence types. Copyright © 2003 John Wiley & Sons, Ltd.
Habituation in high‐risk infants: reliability and patterns of responding
Authors: Brian Jessica A. , Landry Reginald , Szatmari Peter , Niccols Alison , Bryson Susan
Published: September 2003

We examined both the reliability of infant‐controlled habituation and patterns of responding in a group of high‐risk infants (mean age 16 mos). Good test–retest reliability was found for mean, total, and baseline looking time for one of the stimuli. Classification of infants' pattern of performance yielded two groups: linear (57%) and non‐linear (29%) responders; 14% of cases could not be classified because of cross‐session inconsistencies in performance. Linear responders had shorter total looking times, fewer trials to criterion, and showed more habituation than non‐linear responders, thus validating the linear/non‐linear distinction. Our findings indicate that the infant‐controlled habituation task can be used reliably with infants who are at high risk for developmental disorders. Indeed, we provide evidence that this task is not only reliable, but may also provide meaningful distinctions between infants within the high‐risk population. Discussion focuses on the role of attention in distinguishing between short (linear) and long (non‐linear) lookers. Copyright © 2003 John Wiley & Sons, Ltd.
Stable carbon isotope composition of terrestrial leaves: inter‐ and intraspecies variability, cellulose and whole‐leaf tissue difference, and potential for climate reconstruction
Authors: Rundgren Mats , Loader Neil J. , Hammarlund Dan
Published: September 2003

Stable carbon isotope analysis of terrestrial plant leaves preserved in Quaternary lake sediments has the potential to provide high‐resolution reconstructions of past climatic conditions. Preferably, δ13C measurements should be made on a single leaf component, e.g. cellulose, but this approach is often precluded by limited leaf availability. Previous work suggests that reliable palaeoclimatic information also may be derived from δ13C measurements on whole‐leaf tissue, given a similar degree of leaf decomposition between samples. Leaf δ13C data for 12 Scandinavian species of dwarf‐shrubs, shrubs and trees, and a comparison of δ13C data on recent and late Holocene Salix herbacea leaves, revealed that the δ13C signal registered by holocellulose is largely reflected by measurements on whole‐leaf tissue. Holocellulose was found to be consistently enriched in 13C, although this δ13C offset was smaller for subfossil leaves. This supports the use of δ13C measurements on whole‐leaf tissue for climate reconstruction, at least for leaves preserved in soft, late Holocene sediments with minimal diagenetic effects. Leaf carbon and nitrogen data on fresh leaves of the same 12 Scandinavian species, and corresponding data on late Holocene Salix herbacea leaves, suggest that the leaf C:N ratio is a suitable indicator of the degree of leaf decomposition. Copyright © 2003 John Wiley & Sons, Ltd.
Primary gastric Burkitt lymphoma in childhood: Associated with Helicobacter pylori?
Authors: Moschovi Maria , Menegas Damianos , Stefanaki Kalliopi , Constantinidou Catherine Van‐Vliet , Tzortzatou‐Stathopoulou Fotini
Published: September 2003

Background

This retrospective study was designed to estimate the incidence of primary gastric non‐Hodgkin lymphoma (NHL) in childhood and the possible association with Helicobacter pylori (H. pylori).

Procedure

We reviewed and analyzed the charts of 135 patients with NHL that were diagnosed and treated in a single oncology unit during the last 20 years.

Results

Only two patients, 5 and 12 years old, with primary gastric NHL were found. Upper gastroduodenal endoscopy detected an ulcer in the lesser curvature of the body of the stomach, in both cases. Endoscopy revealed a moderate chronic gastritis in the antrum of both patients that was H. pylori associated in one of them who also suffered from chronic gastritis. Biopsy specimens demonstrated infiltration by Burkitt lymphoma (BL). The two patients received chemotherapy for 6 months. Additionally, one of the two patients received a triple therapy regimen with bismuth, amoxicillin, and metronidazole for H. pylori. Fifteen and six years later they are in complete remission, free of symptoms.

Conclusions

Primary gastric NHL in childhood is rare. It was found in fewer than 2% of our NHL patients. The temporal relationship between the H. pylori infection and BL suggest a causative link between these two events. Med Pediatr Oncol 2003;41:444–447. © 2003 Wiley‐Liss, Inc.
Regional cardiac wall motion abnormalities during and shortly after anthracyclines therapy
Authors: Kapusta Livia , Groot‐Loonen Jacqueline , Thijssen Johan M. , deGraaf Ruurd , Daniëls O.
Published: September 2003

Background

Tissue Doppler imaging (TDI) is a new non‐invasive ultrasound technique that enables quantitative assessment of regional myocardial wall motion. A previous study of survivors of childhood malignancies demonstrated abnormalities of regional diastolic wall motion abnormalities many years after treatment with anthracyclines. The purpose of the present study was to investigate this phenomenon during and shortly after treatment.

Procedure

A total of 60 patients, age range 4.4–16.0 years, were included in this study: 43 early survivors, with a mean follow‐up duration of 2.1 (range 0.3–5.2) years from end of anthracycline treatment, were evaluated retrospectively. Seventeen other patients were evaluated before, during, and 6 months after the end of anthracycline therapy. All patients received moderate cumulative doses of anthracyclines (range 120–450 mg/m2). Echocardiographic examination was performed using standardized conventional and TDI techniques.

Results

Of the early survivors, 26 (60%) demonstrated regional LV free wall motion abnormalities. In the prospective group, serial echocardiographic studies revealed three patients (18%) with regional abnormalities of LV free wall motion before starting chemotherapy, but 14 (82%) at the end of treatment. Six months later, however, the incidence decreased to 61% of the survivors. Subject and treatment characteristics, as well as LV wall diameters and fractional shortening were not significantly different for children with or without free wall motion abnormalities. Regional wall motion abnormalities were also seen in the interventricular septum, although this was less frequent.

Conclusions

Regional diastolic wall motion abnormalities are common during and shortly after anthracyclines therapy but may be transient. The authors recommend simultaneous use of both conventional echocardiography & TDI for the monitoring of anthracycline‐induced cardiotoxicity. Med Pediatr Oncol 2003;41:426–435. © 2003 Wiley‐Liss, Inc.
On the nature of modified composite electrical effect parameters
Authors: Charton Marvin , Charton Barbara I.
Published: September 2003

It is shown that a correlation of some property, reactivity or biological activity with pure parameters can also be carried out with composite parameters to produce a model with comparable statistics. Modified composite electrical effect parameters can be obtained from known composite electrical effect parameters by means of an algorithm such as

σX♦ = (σX + c)m

in which σX♦ is the modified composite electrical effect parameter (MCEEP), σX the original composite electrical effect parameter, c a constant and m an exponent. MCEEPs were calculated from this equation with c equal to 2 and m ranging from −4 to 4 when σX is σm or σp, and from −2 to 2 when it is σp+. They were used to model 10 sets of chemical reactivities that had previously been correlated with the pure parameters σ1, σd and σe, which represent the localized (field), intrinsic delocalized (resonance) and electronic demand sensitivity electrical effects, respectively. In most cases both the pure and the modified composite parameters give comparable fits to the data as measured by the values of 100R2, in accord with the prediction. The composition of the MCEEPs was a linear function of m. The advantage in using pure parameters is that they are readily interpretable. Correlations with composite parameters can be interpreted only if their composition has been determined. These results provide an understanding of the way in which topological parameters work. Copyright © 2003 John Wiley & Sons, Ltd.
Hydride abstraction from 1,3,5‐cycloheptatriene by gaseous carbenium ions, as studied by Fourier transform ion cyclotron resonance kinetics and deuterium labeling
Authors: Mormann Michael , Kuck Dietmar
Published: September 2003

The gas‐phase interaction of protonated acetone and tert‐butyl cations with 1,3,5‐cycloheptatriene was studied by Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometry. In addition to proton transfer giving C7H9+ ions, hydride abstraction from cycloheptatriene giving C7H7+ ions was observed. Deuterium labeling experiments combined with the determination of the reaction kinetics excluded the formation of C7H7+ ions by consecutive proton transfer and H2 expulsion under these conditions. The kinetic isotope effect measured for the hydride transfer channel was found to be in the range 1.65±0.1, very close to that known to operate during hydride transfer from simple alkylbenzenes to t‐C4H9+ ions. Copyright © 2003 John Wiley & Sons, Ltd.