bluuebunny/crossref_metadata_2025 huggingface dataset:
Light emission from cBN crystal synthesized at high pressure and high temperature
Authors: Dou Qing-Ping , Ma Hai-Tao , Jia Gang , Chen Zhan-Guo , Cao Kun , Ren Ce , Zhao Jian-Xun , Liu Xiu-Huan , Zhang Yu-Hong , Shi Bao , Zhang Tie-Chen
Published: April 2006

The light emission at a wavelength of about 400nm is observed from the nonintentionally doped n-cubic boron nitride crystal, when the avalanche breakdown occurs inside the cBN crystal that is prepared by hexagonal boron nitride at high pressure and high temperature using nitride as catalyst. The measured spectrum has a peak in the blue-violet range. It shows the electronic transition between valleys of the conduction band of the cBN crystal. At the same time, the current-controlled differential negative resistance phenomenon occurs as well.
Self-strain of solids with spherical nanovoids
Authors: He L. H.
Published: April 2006

We study surface stress-induced self-strain of elastically isotropic solids with nanovoids. When the voids are spherically shaped and of identical size, we show that certain hydrostatic loads applied on the outer surface can create uniform stress and strain fields within such solids. The result is then used to establish an exact link between the self-strain and the effective elastic property of the solid, provided that the voids are distributed such that the solid is statistically homogeneous on macroscopic level.
Characterization of focused-ion-beam-induced damage in n-type silicon using Schottky contact
Authors: Xia Ling , Wu Wengang , Hao Yilong , Wang Yangyuan , Xu Jun
Published: April 2006

The effects of focused-ion-beam-induced damage on electrical properties of n-type Si are investigated by Schottky contacts. Crystalline Si is exposed to 10–30keV focused ion beam (FIB), followed by Pt deposition under vacuum of 4×10−4Pa. From current-voltage-temperature measurements, barrier heights of the Schottky contacts are found to increase almost linearly as the FIB energy increases, with the maximum increment of 0.29eV. The increase is suggested to be related to the arising of acceptorlike defects and an amorphous layer due to FIB damages. A theoretical model is set up to quantitatively describe the barrier height changes.
Laser-induced short- and long-range orderings of Co nanoparticles on SiO2
Authors: Favazza C. , Trice J. , Krishna H. , Kalyanaraman R. , Sureshkumar R.
Published: April 2006

Laser irradiation of ultrathin Co films leads to pattern formation by dewetting with short-range order (SRO) as well as long-range order (LRO). When a 1.5nm thick Co film is irradiated by a single laser beam, a monomodal size distribution of particles with average diameter of 31±10nm and nearest-neighbor spacing of 75nm is observed. Moreover, melting by two-beam interference irradiation produces LRO as well as SRO giving a quasi-two-dimensional arrangement of nanoparticles. The SRO is attributed to spinodal dewetting while the LRO is conjectured to be induced by in-plane interfacial tension gradients. Laser-induced dewetting of metals could be a simple technique to fabricate ordered metal nanoarrays.
Vessel-related mortality of sea turtles in Queensland, Australia
Authors: Hazel Julia , Gyuris Emma
Published: April 2006

Identification of threats is a standard component of conservation planning and the ability to rank threats may improve the allocation of scarce resources in threat-mitigation programs. For vulnerable and endangered sea turtles in Australia, vessel strike is recognised as an important threat but its severity relative to other threats remains speculative. Documented evidence for this problem is available only in stranding records collected by the Queensland Environment Protection Authority. With the authority’s support we assessed the scope and quality of the data and analysed vessel-related records. We found adequate evidence that during the period 1999–2002 at least 65 turtles were killed annually as a result of collisions with vessels on the Queensland east coast. This level of mortality appears broadly comparable to that recorded in the Queensland East Coast Trawl Fishery before the introduction of mandatory turtle-exclusion devices in that fishery. Green turtles (Chelonia mydas) comprised the majority of vessel-related records, followed by loggerhead turtles (Caretta caretta), and 72% of cases concerned adult or subadult turtles. The majority of vessel-related records came from the greater Moreton Bay area, followed by Hervey Bay and Cleveland Bay. The waters of all three areas are subject to variable levels of commercial and recreational vessel traffic, and their shores are both populated and unpopulated.
DNA motifs in human and mouse proximal promoters predict tissue-specific expression
Authors: Smith Andrew D. , Sumazin Pavel , Xuan Zhenyu , Zhang Michael Q.
Published: April 2006

Comprehensive identification of cis-regulatory elements is necessary for accurately reconstructing gene regulatory networks. We studied proximal promoters of human and mouse genes with differential expression across 56 terminally differentiated tissues. Using
in silico
techniques to discover, evaluate, and model interactions among sequence elements, we systematically identified regulatory modules that distinguish elevated from inhibited expression in the corresponding transcripts. We used these putative regulatory modules to construct a single predictive model for each of the 56 tissues. These predictors distinguish tissue-specific elevated from inhibited expression with statistical significance in 80% of the tissues (45 of 56). The predictors also reveal synergy between cis-regulatory modules and explain large-scale tissue-specific differential expression. For testis and liver, the predictors include computationally predicted motifs. For most other tissues, the predictors reveal synergy between experimentally verified motifs and indicate genes that are regulated by similar tissue-specific machinery. The identification in proximal promoters of cis-regulatory modules with tissue-specific activity lays the groundwork for complete characterization and deciphering of cis-regulatory DNA code in mammalian genomes.
Breakpoint structure reveals the unique origin of an interspecific chromosomal inversion (
2La
) in the
Anopheles gambiae
complex
Authors: Sharakhov Igor V. , White Bradley J. , Sharakhova Maria V. , Kayondo Jonathan , Lobo Neil F. , Santolamazza Federica , della Torre Alessandra , Simard Frédéric , Collins Frank H. , Besansky Nora J.
Published: April 2006

Paracentric chromosomal inversions are major architects of organismal evolution and have been associated with adaptations relevant to malaria transmission in anopheline mosquitoes. The processes responsible for their origin and maintenance, still poorly understood, can be illuminated by analysis of inversion breakpoint sequences. Here, we report the breakpoint structure of chromosomal inversion
2La
from the principal malaria vector
Anopheles gambiae
and its relatives in the
A. gambiae
complex. The distal and proximal breakpoints of the standard (
2L
+

a

) arrangement contain gene duplications: full-length genes and their truncated copies at opposite ends. Intact genes without pseudogene copies in the alternative arrangement (
2La
) imply that
2L
+

a

is derived and was viable despite damage to genes, because duplication preserved gene function. A unique origin for the interspecific
2La
inversion was challenged previously by indirect genetic evidence, but breakpoint sequences determined from members of the
A. gambiae
complex strongly suggest their descent from a single event. The derived position of
2L
+

a

, long considered ancestral in this medically important group, has significant implications for the phylogenetic history and the evolution of vectorial capacity in the
A. gambiae
complex.
Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina
Authors: Roberts Melanie R. , Srinivas Maya , Forrest Douglas , Morreale de Escobar Gabriella , Reh Thomas A.
Published: April 2006

Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. The number and spatial organization of cone types varies dramatically among species, presumably to fine-tune the retina for different visual environments. In the mouse, S- and M-opsin are expressed in an opposing dorsal–ventral gradient. We previously reported that cone opsin patterning requires thyroid hormone β2, a nuclear hormone receptor that regulates transcription in conjunction with its ligand, thyroid hormone (TH). Here we show that exogenous TH inhibits S-opsin expression, but activates M-opsin expression. Binding of endogenous TH to TRβ2 is required to inhibit S-opsin and to activate M-opsin. TH is symmetrically distributed in the retina at birth as S-opsin expression begins, but becomes elevated in the dorsal retina at the time of M-opsin onset (postnatal day 10). Our results show that TH is a critical regulator of both S-opsin and M-opsin, and suggest that a TH gradient may play a role in establishing the gradient of M-opsin. These results also suggest that the ratio and patterning of cone types may be determined by TH availability during retinal development.
Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism
Authors: Pitteloud Nelly , Acierno James S. , Meysing Astrid , Eliseenkova Anna V. , Ma Jinghong , Ibrahimi Omar A. , Metzger Daniel L. , Hayes Frances J. , Dwyer Andrew A. , Hughes Virginia A. , Yialamas Maria , Hall Janet E. , Grant Ellen , Mohammadi Moosa , Crowley William F.
Published: April 2006

Mutations in
KAL1
and
FGFR1
cause Kallmann syndrome (KS), whereas mutations in the
GNRHR
and
GPR54
genes cause idiopathic hypogonadotropic hypogonadism with normal olfaction (nIHH). Mixed pedigrees containing both KS and nIHH have also been described; however, the genetic cause of these rare cases is unknown. We examined the
FGFR1
gene in seven nIHH subjects who either belonged to a mixed pedigree (
n
= 5) or who had associated midline defects (
n
= 2). Heterozygous
FGFR1
mutations were found in three of seven unrelated nIHH probands with normal MRI of the olfactory system: (
i
) G237S in an nIHH female and a KS brother; (
ii
) (P722H and N724K) in an nIHH male missing two teeth and his mother with isolated hyposmia; and (
iii
) Q680X in a nIHH male with cleft lip/palate and missing teeth, his brother with nIHH, and his father with delayed puberty. We show that these mutations lead to receptor loss-of-function. The Q680X leads to an inactive FGFR1, which lacks a major portion of the tyrosine kinase domain (TKD). The G237S mutation inhibits proper folding of D2 of the FGFR1 and likely leads to the loss of cell-surface expression of FGFR1. In contrast, the (P722H and N724K) double mutation causes structural perturbations in TKD, reducing the catalytic activity of TKD. We conclude that loss-of-function mutations in
FGFR1
cause nIHH with normal MRI of the olfactory system. These mutations also account for some of the mixed pedigrees, thus challenging the current idea that KS and nIHH are distinct entities.
mGluR2 acts through inhibitory Gα subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses
Authors: Nicholls Russell E. , Zhang Xiao-lei , Bailey Christopher P. , Conklin Bruce R. , Kandel Eric R. , Stanton Patric K.
Published: April 2006

Presynaptic inhibitory G protein-coupled receptors play a critical role in regulating transmission at a number of synapses in the central and peripheral nervous system. We generated transgenic mice that express a constitutively active form of an inhibitory Gα subunit to examine the molecular mechanisms underlying the actions of one such receptor, metabotropic glutamate receptor (mGluR) 2, at mossy fiber-CA3 synapses in the hippocampus. mGluR2 participates in at least three types of mossy fiber synaptic plasticity, (
i
) transient suppression of synaptic transmission, (
ii
) long-term depression (LTD), and (
iii
) inhibition of long-term potentiation (LTP), and we find that inhibitory Gα signaling is sufficient to account for the actions of mGluR2 in each. The fact that constitutively active Gα
i2
occludes the transient suppression of synaptic transmission by mGluR2, while enhancing LTD, suggests further that these two forms of plasticity are expressed via different mechanisms. In addition, the LTP deficit observed in constitutively active Gα
i2
-expressing mice suggests that mGluR2 activation may serve as a metaplastic switch to permit the induction of LTD by inhibiting LTP.
Identification of small molecules that induce apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation
Authors: Mo Hao , Henriksson Marie
Published: April 2006

The Myc transcription factor plays a central role in the regulation of cell cycle progression, apoptosis, angiogenesis, and cellular transformation. Myc is a potent oncoprotein that is deregulated in a wide variety of human tumors and is therefore an attractive target for novel cancer therapies. Using a cellular screening approach, we have identified low-molecular-weight compounds, Myc pathway response agents (MYRAs), that induce apoptosis in a c-Myc-dependent manner and inhibit Myc-driven cellular transformation. MYRA-A inhibits Myc transactivation and interferes with the DNA-binding activity of Myc family proteins but has no effect on the E-box-binding protein USF. In contrast, MYRA-B induces Myc-dependent apoptosis without affecting Myc transactivation or Myc/Max DNA binding. Our data show that cellular screening assays can be a powerful strategy for the identification of candidate substances that modulate the Myc pathway. These compounds can be useful tools for studying Myc function and may also be of therapeutic potential as leads for drug development.
Toll-like receptor 4 plays a crucial role in the immune–adrenal response to systemic inflammatory response syndrome
Authors: Zacharowski Kai , Zacharowski Paula A. , Koch Alexander , Baban Aida , Tran Nguyen , Berkels Reinhard , Papewalis Claudia , Schulze-Osthoff Klaus , Knuefermann Pascal , Zähringer Ulrich , Schumann Ralf R. , Rettori Valeria , McCann Samuel M. , Bornstein Stefan R.
Published: April 2006

Sepsis and septic shock are leading killers in the noncoronary intensive care unit, and they remain worldwide health concerns. The initial host defense against bacterial infections involves Toll-like receptors (TLRs), which detect and respond to microbial ligands. In addition, a coordinated response of the adrenal and immune systems is crucial for survival during severe inflammation. Previously, we demonstrated a link between the innate immune system and the endocrine stress response involving TLR-2. Like TLR-2, TLR-4 is also expressed in human and mouse adrenals. In the present work, by using a low dose of LPS to mimic systemic inflammatory response syndrome, we have revealed marked cellular alterations in adrenocortical tissue and an impaired adrenal corticosterone response in TLR-4−/−mice. Our findings demonstrate that TLR-4 is a key mediator in the crosstalks between the innate immune system and the endocrine stress response. Furthermore, TLR polymorphisms could contribute to the underlying mechanisms of impaired adrenal stress response in patients with bacterial sepsis.
The mechanism of M.HhaI DNA C5 cytosine methyltransferase enzyme: A quantum mechanics/molecular mechanics approach
Authors: Zhang Xiaodong , Bruice Thomas C.
Published: April 2006

The mechanism of DNA cytosine-5-methylation catalyzed by the bacterial M.HhaI enzyme has been considered as a stepwise nucleophilic addition of Cys-81-S
−
to cytosine C6 followed by C5 nucleophilic replacement of the methyl of
S
-adenosyl-
l
-methionine to produce 5-methyl-6-Cys-81-S-5,6-dihydrocytosine. In this study, we show that the reaction is concerted from a series of energy calculations by using the quantum mechanical/molecular mechanical hybrid method. Deprotonation of 5-methyl-6-Cys-81-S-5,6-dihydrocytosine and expulsion of Cys-81-S
−
provides the product DNA 5-methylcytosine. A required base catalyst for this deprotonation is not available as a member of the active site structure. A water channel between the active site and bulk water allows entrance of solvent to the active site. Hydroxide at 10
−7
mole fraction (pH = 7) is shown to be sufficient for the required catalysis. We also show that Glu-119-CO
2
H can divert the reaction by protonating cytosine N3 when Cys-81-S
−
attacks cytosine, to form the 6-Cys-81-S-3-hydrocytosine. The reactants and 6-Cys-81-S-3-hydrocytosine product are in rapid equilibrium, and this explains the observed hydrogen exchange of cytosine with solvent.
Nanoindentation studies of full and empty viral capsids and the effects of capsid protein mutations on elasticity and strength
Authors: Michel J. P. , Ivanovska I. L. , Gibbons M. M. , Klug W. S. , Knobler C. M. , Wuite G. J. L. , Schmidt C. F.
Published: April 2006

The elastic properties of capsids of the cowpea chlorotic mottle virus have been examined at pH 4.8 by nanoindentation measurements with an atomic force microscope. Studies have been carried out on WT capsids, both empty and containing the RNA genome, and on full capsids of a salt-stable mutant and empty capsids of the subE mutant. Full capsids resisted indentation more than empty capsids, but all of the capsids were highly elastic. There was an initial reversible linear regime that persisted up to indentations varying between 20% and 30% of the diameter and applied forces of 0.6–1.0 nN; it was followed by a steep drop in force that is associated with irreversible deformation. A single point mutation in the capsid protein increased the capsid stiffness. The experiments are compared with calculations by finite element analysis of the deformation of a homogeneous elastic thick shell. These calculations capture the features of the reversible indentation region and allow Young's moduli and relative strengths to be estimated for the empty capsids.
Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy
in vivo
Authors: Farokhzad Omid C. , Cheng Jianjun , Teply Benjamin A. , Sherifi Ines , Jon Sangyong , Kantoff Philip W. , Richie Jerome P. , Langer Robert
Published: April 2006

Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using prostate cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(
d
,
l
-lactic-
co
-glycolic acid)-
block
-poly(ethylene glycol) (PLGA-
b
-PEG) copolymer and surface functionalized with the A10 2′-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), a well characterized antigen expressed on the surface of prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced
in vitro
cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (
P
< 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean body weight loss (BWL)
in vivo
[body weight loss of 7.7 ± 4% vs. 18 ± 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir, respectively (mean ± SD);
n
= 7]. After a single intratumoral injection of Dtxl-NP-Apt bioconjugates, complete tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial tumor volume of ≈300 mm
3
), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application.
Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis
Authors: Gong Yi , Lee Joon No , Brown Michael S. , Goldstein Joseph L. , Ye Jin
Published: April 2006

Insig-1 and Insig-2 are closely related proteins of the endoplasmic reticulum (ER) that mediate feedback control of cholesterol synthesis by sterol-dependent binding to the following two membrane proteins: the escort protein Scap, thus preventing proteolytic processing of sterol regulatory element-binding proteins; and the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase, thus inducing the ubiquitination and ER-associated degradation of the enzyme. Here, we report that the conserved Asp-205 in Insig-1, which abuts the fourth transmembrane helix at the cytosolic side of the ER membrane, is essential for its dual function. When Asp-205 was mutated to alanine, the mutant Insig-1 lost the ability to bind to Scap and, thus, was unable to suppress the cleavage of sterol regulatory element-binding proteins. The mutant Insig-1 was ineffective also in accelerating sterol-stimulated degradation of 3-hydroxy-3-methylglutaryl CoA reductase. Alanine substitution of the corresponding aspartic acid in Insig-2 produced the same dual defects. These studies identify a single amino acid residue that is crucial for the function of Insig proteins in regulating cholesterol homeostasis in mammalian cells.
In vitrofolate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes
Authors: Lin Hui-Li , Chen Chung-Jern , Tsai Wen-Chan , Yen Jeng-Hsien , Liu Hong-Wen
Published: April 2006

Invitrofolate deficiency is associated with S phase accumulation and apoptosis in various cell types. To investigate the role of p53 and two apoptosis-related molecules, bcl-2 and Fas antigen (Apo-1, CD95), in the mechanism whereby folate-deficient lymphocytes accumulate and undergo apoptosis in the S phase, normal human peripheral blood lymphocytes were cultured for 3–9 d in control medium or in specially ordered and formulated HAM’ F-10 medium lacking folic acid, thymidine and hypoxanthine. Cells were stimulated with phytohaemagglutinin for the final 72 h prior to harvesting. The results indicate that p53 expression was downregulated in folate-deficient lymphocytes when compared with the control lymphocytes during the relevant period of S phase accumulation and apoptosis. In addition, folate deficiency was also found to downregulate IL-2, Fas antigen and bcl-2 expression, in terms of either mRNA or protein levels. The downregulation of Fas antigen suggests that folate deficiency-induced apoptosis probably does not occur via the Fas pathway. As IL-2 is a known inducer of bcl-2, and the downregulation of bcl-2 induces apoptosis, the downregulation of IL-2 and bcl-2 is suggested to play an important role in apoptosis. The complete rescue of folate-deficient lymphocytes from apoptosis was achieved by folic acid, thymidine or hypoxanthine alone or thymidine and hypoxanthine in combination. These results suggest that IL-2 depletion by folate deficiency in lymphocytes reduces the bcl-2 level, thereby triggering deoxynucleoside triphosphate pool imbalance and p53-independent apoptosis.
Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism
Authors: Hirche F. , Schröder A. , Knoth B. , Stangl G. I. , Eder K.
Published: April 2006

Methionine has been shown to increase plasma cholesterol in animals. In the present study, mechanisms were investigated by which methionine could alter cholesterol metabolism. In the first experiment, forty growing rats were fed four casein-based diets differing in methionine content (2·6, 3·5, 4·5 or 6·0 g/kg) for 14 d. In the second experiment, isolated rat hepatocytes were incubated in media supplemented with 50, 100 or 200 μmol/l methionine. Dietary methionine tended to increase plasma homocysteine concentrations in the rats (P=0·058). A weak positive correlation between circulating homocysteine and plasma cholesterol was observed (R20·27, P<0·01). Rats fed 3·5 g/kg or more of methionine had higher concentrations of cholesterol in their plasma, in lipoprotein fractions of density (ρ kg/l) 1·006 < ρ<, 1·063 and ρ>. 1·063, and in liver than rats fed 2·6 g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7α-hydroxylase than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine ratio in rat liver increased with rising dietary methionine concentration; the relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and cystathionine β-synthase remained unaffected. Hepatocytes incubated in media supplemented with 100 or 200 μmol/l methionine had a higher cholesterol synthesis than hepatocytes incubated in a medium supplemented with 50μmol/l methionine; the LDL uptake in hepatocytes was independent of the methionine concentration of the medium. In conclusion, the present study suggests that dietary methionine induces hypercholesterolaemia at least in part via an enhanced hepatic cholesterol synthesis.
Biochemical hepatic alterations and body lipid composition in the herbivorous grass carp (Ctenopharyngodon idella) fed high-fat diets
Authors: Du Zhen-Yu , Clouet Pierre , Zheng Wen-Hui , Degrace Pascal , Tian Li-Xia , Liu Yong-Jian
Published: April 2006

High-fat diets may have favourable effects on growth of some carnivorous fish because of the protein-sparing effect of lipids, but high-fat diets also exert some negative impacts on flesh quality. The goal of the study was therefore to determine the effects of fat-enriched diets in juvenile grass carp (Ctenopharyngodon idella) as a typical herbivorous fish on growth and possible lipid metabolism alterations. Three isonitrogenous diets containing 2, 6 or 10% of a mixture of lard, maize oil and fish oil (1:1:1, by weight) were applied to fish for 8 weeks in a recirculation system. Data show that feeding diets with increasing lipid levels resulted in lowered feed intake, decreased growth and feed efficiency, and increased mesenteric fat tissue weight. Concomitantly, alteration of lipoprotein synthesis and greater level of lipid peroxidation were apparent in blood. In liver, muscle and mesenteric fat tissue, the percentages of α-linolenic acid and DHA were significantly increased or tended to increase with higher dietary lipid levels. Biochemical activity measurements performed on liver showed that, with the increase in dietary lipid level, there was a decrease in both mitochondrial and peroxisomal fatty acid oxidation capacities, which might contribute, at least in part, to the specific accumulation of α-linolenic acid and DHA into cells more active in membrane building. On the whole, grass carp have difficulty in energetically utilising excess dietary fat, especially when enriched in n−3 PUFA that are susceptible to peroxidation.
Effect of potato on acid–base and mineral homeostasis in rats fed a high-sodium chloride diet
Authors: Narcy Agnés , Robert Laetitia , Mazur Andrzej , Demigné Christian , Rémésy Christian
Published: April 2006

Excessive dietary NaCl in association with a paucity of plant foods, major sources of K alkaline salts, is a common feature in Western eating habits which may lead to acid–base disorders and to Ca and Mg wasting. In this context, to evaluate the effects of potato, rich in potassium citrate, on acid–base homeostasis and mineral retention, Wistar rats were fed wheat starch (WS) or cooked potato (CP) diets with a low (0·5 %) or a high (2 %) NaCl content during 3 weeks. The replacement of WS by CP in the diets resulted in a significant urinary alkalinisation (pH from 5·5 to 7·3) parallel to a rise in citrate and K excretion. Urinary Ca and Mg elimination represented respectively 17 and 62% of the daily absorbed mineral in rats fed the high-salt WS diet compared with 5 and 28% in rats fed the high-salt CP diet. The total SCFA concentration in the caecum was 3-fold higher in rats fed the CP diets compared with rats fed the WS diets, and it led to a significant rise in Ca and Mg intestinal absorption (Ca from 39 to 56 %; Mg from 37 to 60 %). The present model of low-grade metabolic acidosis indicates that CP may be effective in alkalinising urine, enhancing citrate excretion and ameliorating Ca and Mg balance.
Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity
Authors: Oku Tsuneyuki , Yamada Mai , Nakamura Mariko , Sadamori Naoki , Nakamura Sadako
Published: April 2006

The inhibitory effect on human and rat intestinal disaccharidase by the extractive from the leaves ofMorus alba (ELM) containing 0·24% 1-deoxynojirimycin equivalent and its inhibitory activities were investigated by the modified Dahlqvist method. In the presence of 1000-fold diluted ELM solution, the sucrase activity of four human samples was inhibited by 96% and that of maltase and isomaltase by 95 and 99 %, respectively. The activities of trehalase and lactase were inhibited by 44 and 38 %, respectively. The human disaccharidase activities varied from sample to sample because the samples were obtained from different resected regions after surgery. However, the ratio of the inhibitory effect for sucrase, maltase, isomaltase, trehalase and lactase was very similar among the four samples, and also that of resembled rat intestinal disaccharides. The inhibitory constant of the 1-deoxynojirimycin equivalent for sucrase, maltase and isomaltase was 2·1× 10−4, 2·5 × 10−4 and 4·5 10−4μM, respectively, and these inhibitory activities were shown, using rat brush border membrane vesicles, to be competitive. These results demonstrate that digestion is inhibited when an appropriate amount of ELM is orally ingested with sucrose or polysaccharide in man. When ELM was orally administered in a sucrose solution to fasted rats, the elevation in blood glucose was significantly suppressed, depending on the concentration of ELM given. These results suggest that ELM could be used as an ingredient in health foods and in foods that help to prevent diabetes.
Hypocholesterolaemic effects of milk-kefir and soyamilk-kefir in cholesterol-fed hamsters
Authors: Liu Je-Ruei , Wang Sheng-Yao , Chen Ming-Ju , Chen Hsiao-Ling , Yueh Pei-Ying , Lin Chin-Wen
Published: April 2006

This study aimed to evaluate the hypocholesterolaemic property of milk-kefir and soyamilk-kefir. Male hamsters were fed on a cholesterol-free or cholesterol-enriched diet containing 10% skimmed milk, milk-kefir, soyamilk or soyamilk-kefir for a period of 8 weeks. The soyamilk, milk-kefir and soyamilk-kefir diets all tended towards a lowering of serum triacylglycerol and total cholesterol concentrations, and a reduction of cholesterol accumulation in the liver, the decrease in serum cholesterol concentration being mainly in the non-HDL fraction. The soyamilk-kefir diet led to a significant increase in the faecal excretion of neutral sterols and bile acids compared with the other two diets. The soyamilk-kefir diet also elicited a significant decrease in the serum ratio of non-HDL-cholesterol to HDL-cholesterol, compared with the control, than was the case for the other diets. These findings demonstrate that soyamilk-kefir may be considered to be among the more promising food components in terms of preventing CVD through its hypocholesterolaemic action.
Divergent effects of quercetin conjugates on angiogenesis
Authors: Donnini Sandra , Finetti Federica , Lusini Lorenzo , Morbidelli Lucia , Cheynier Veronique , Barron Denis , Williamson Gary , Waltenberger Johannes , Ziche Marina
Published: April 2006

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3′-sulphate (Q3′S) and quercetin-3-glucuronide (Q3G)) onin vivoangiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3′Sper sepromoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3′S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G andQ3′S are the two major conjugates in plasma, but their ratio is dependenton several factors, so thatinhibition or activation of angiogenesis could be subtly shifted as a result of metabolismin vivo.
Evidence for impaired insulin production and higher sensitivity in stunted children living in slums
Authors: Martins P. A , Sawaya A. L.
Published: April 2006

The objective of the present study was to investigate the changes in glucose and insulin metabolism in nutritionally stunted children that can be involved in the appearance of chronic diseases in adulthood. For this purpose, sixty-one children were selected, thirty-five boys and twenty-six girls, residents of slums in S˜o Paulo, Brazil. The children were classified according to the height-for-age as stunted (1·5 Z-score; n 21) or non-stunted (≥1·5 Z-score; n 40). The glucose and insulin plasma levels were determined and, from these values, the indexes that evaluate the pancreatic ·-cell function (homeostasis model assessment (HOMA-B)) and insulin sensitivity (HOMA-S) were assessed. Stunted children showed lower values of fasting insulin than those of the non-stunted group (boys: 29·7 (SD 14·9) v. 5=·4 (SD 29·2) pmol/l, P=·019; girls: 34·4 (SD 12·6) v. 62·3 (SD 28·7) pmol/l, P=·016) but the glucose levels were similar (boys: 4·6 (SD =·3) v. 4·5 (SD =·3) mmol/l; girls: 4·2 (SD =·3) v. 4·4 (SD =·3) mmol/l). Stunted children showed lower HOMA-B values (boys: 83 (SD 22) % v. 115 (SD 36) %, P=·011; girls: 107 (SD 23) % v. 144 (SD 46) %, P=·045) and higher HOMA-S values (boys: 196 (SD 92) % v. 120 (SD 62) %, P=·014; girls: 159 (SD 67) % v· 98 (SD 57) %, P=·016). The results show a decreased activity of μ-cell function and increased insulin sensitivity in stunted children. The decreased b-cell function of this group may strongly predict type 2 diabetes.
Childhood obesity treatment: targeting parents exclusivelyv.parents and children
Authors: Golan Moria , Kaufman Vered , Shahar Danit R.
Published: April 2006

There is a consensus that interventions to prevent and treat childhood obesity should involve the family; however, the extent of the child's involvement has received little attention. The goal of the present study was to evaluate the relative efficacy of treating childhood obesity via a family-based health-centred intervention, targeting parents alonev. parents and obese children together. Thirty-two families with obese children of 6–11 years of age were randomised into groups, in which participants were provided for 6 months a comprehensive educational and behavioural programme for a healthy lifestyle. These groups differed in their main agent of change: parents-onlyv. the parents and the obese child. In both groups, parents were encouraged to foster authoritative parenting styles (parents are both firm and supportive; assume a leadership role in the environmental change with appropriate granting of child's autonomy). Only the intervention aimed at parents-only resulted in a significant reduction in the percentage overweight at the end of the programme (P=0·02) as well as at the 1-year follow-up meeting.The differences between groups at both times were significant (P<0·05). A greater reduction in food stimuli in the home (P<0·05) was noted in the parents-only group. In both groups, the parents' weight status did not change. Regression analysis shows that the level of attendance in sessions explained 28% of the variability in the children's weight status change, the treatment group explained another 10%, and the improvement in the obesogenic load explained 11% of the variability. These results suggest that omittingthe obese child from active participation in the health-centred programme may be beneficial for weight loss and for the promotion of a healthy lifestyle among obese children.
Bioethics in human nutrigenomics research: European Nutrigenomics Organisation workshop report
Authors: Bergmann Manuela M. , Bodzioch Marek , Bonet M. Luisa , Defoort Catherine , Lietz Georg , Mathers John C.
Published: April 2006

As part of its work on setting standards and establishing guidelines for nutrigenomics research, the European Nutrigenomics Organisation (NuGO) is developing bioethical guidelines for those engaged in human nutrigenomics studies. A NuGO working group developed a set of draft guidelines addressing four areas: (1) information and consenting prior to a nutrigenomicsstudy; (2) the generation and use of genotype information; (3) the establishment and maintenance of biobanks; (4) the exchange of samples and data. NuGO convened a workshop with a panel of invited external experts to assess the draft guidelines. The panel of experts confirmedthat these areas are important and that the development of specific bioethical guidelines for nutrigenomics research would therefore enhance the application of established international guidelines in this field of biomedical research.
An unusual renal vascular anomaly: common origin of arteries to the lower poles demonstrated by a computed tomography angiography using 16-slice multidetector computed tomography
Authors: Shimada K. , Ohashi I. , Sakai Y. , Kijima T. , Yoshida S. , Okuno T. , Hanafusa K. , Shibuya H.
Published: April 2006

Arterial connection between the left and right kidneys is extremely rare. Only eight cases of such anomalous conditions have been reported in the world literature and all were confirmed by invasive angiography or dissection. We report a patient with this vascular anomaly clearly demonstrated by 16-slice multidetector computed tomography.
Evolution of the imaging tests in hemophilia with emphasis on radiography and magnetic resonance imaging
Authors: Kilcoyne R. F. , Lundin B. , Pettersson H.
Published: April 2006

Even before the discovery of X-rays in 1895 attempts were being made to classify the joint destruction that occurs in hemophilic arthropathy. The advent of radiography added impetus to the search for the optimum classification system. Subsequent attempts have included advanced imaging methods, especially magnetic resonance imaging (MRI). Because of its high spatial resolution and ability to visualize soft tissue abnormalities, MRI is ideally suited as the best way to classify arthropathy. A literature search was carried out to document and list all the imaging methods for hemophilic arthropathy that have been published up to the present. All published classification systems are discussed and listed in tables. MRI has superior imaging capability and will probably become the most important modality for radiological classification of hemophilic arthropathy in the future.
B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma
Authors: Kryczek Ilona , Zou Linhua , Rodriguez Paulo , Zhu Gefeng , Wei Shuang , Mottram Peter , Brumlik Michael , Cheng Pui , Curiel Tyler , Myers Leann , Lackner Andrew , Alvarez Xavier , Ochoa Augusto , Chen Lieping , Zou Weiping
Published: April 2006

Tumor-associated macrophages are a prominent component of ovarian cancer stroma and contribute to tumor progression. B7-H4 is a recently identified B7 family molecule. We show that primary ovarian tumor cells express intracellular B7-H4, whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor macrophages, but not primary ovarian tumor cells, suppress tumor-associated antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and IL-10 are found in high concentrations in the tumor microenvironment. These cytokines stimulate macrophage B7-H4 expression. In contrast, granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4 makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a novel suppressor cell population in ovarian cancer. B7-H4 expression represents a critical checkpoint in determining host responses to dysfunctional cytokines in ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may represent novel strategies to enhance T cell tumor immunity in cancer.
Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection
Authors: Molofsky Ari B. , Byrne Brenda G. , Whitfield Natalie N. , Madigan Cressida A. , Fuse Etsu T. , Tateda Kazuhiro , Swanson Michele S.
Published: April 2006

To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1β secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection.
Endogenous factors enhance HIV infection of tissue naive CD4 T cells by stimulating high molecular mass APOBEC3G complex formation
Authors: Kreisberg Jason F. , Yonemoto Wes , Greene Warner C.
Published: April 2006

Human immunodeficiency virus (HIV) can infect resting CD4 T cells residing in lymphoid tissues but not those circulating in peripheral blood. The molecular mechanisms producing this difference remain unknown. We explored the potential role of the tissue microenvironment and its influence on the action of the antiviral factor APOBEC3G (A3G) in regulating permissivity to HIV infection. We found that endogenous IL-2 and -15 play a key role in rendering resident naive CD4 T cells susceptible to HIV infection. Infection of memory CD4 T cells also requires endogenous soluble factors, but not IL-2 or -15. A3G is found in a high molecular mass complex in HIV infection–permissive, tissue-resident naive CD4 T cells but resides in a low molecular mass form in nonpermissive, blood-derived naive CD4 T cells. Upon treatment with endogenous soluble factors, these cells become permissive for HIV infection, as low molecular mass A3G is induced to assemble into high molecular mass complexes. These findings suggest that in lymphoid tissues, endogenous soluble factors, likely including IL-2 and -15 and others, stimulate the formation of high molecular mass A3G complexes in tissue-resident naive CD4 T cells, thereby relieving the potent postentry restriction block for HIV infection conferred by low molecular mass A3G.
Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
Authors: Paus Didrik , Phan Tri Giang , Chan Tyani D. , Gardam Sandra , Basten Antony , Brink Robert
Published: April 2006

B cells responding to T-dependent antigen either differentiate rapidly into extrafollicular plasma cells or enter germinal centers and undergo somatic hypermutation and affinity maturation. However, the physiological cues that direct B cell differentiation down one pathway versus the other are unknown. Here we show that the strength of the initial interaction between B cell receptor (BCR) and antigen is a primary determinant of this decision. B cells expressing a defined BCR specificity for hen egg lysozyme (HEL) were challenged with sheep red blood cell conjugates of a series of recombinant mutant HEL proteins engineered to bind this BCR over a 10,000-fold affinity range. Decreasing either initial BCR affinity or antigen density was found to selectively remove the extrafollicular plasma cell response but leave the germinal center response intact. Moreover, analysis of competing B cells revealed that high affinity specificities are more prevalent in the extrafollicular plasma cell versus the germinal center B cell response. Thus, the effectiveness of early T-dependent antibody responses is optimized by preferentially steering B cells reactive against either high affinity or abundant epitopes toward extrafollicular plasma cell differentiation. Conversely, responding clones with weaker antigen reactivity are primarily directed to germinal centers where they undergo affinity maturation.
Coupling Modes and Stoichiometry of Cl−/HCO3− Exchange by slc26a3 and slc26a6
Authors: Shcheynikov Nikolay , Wang Youxue , Park Meeyoung , Ko Shigeru B.H. , Dorwart Michael , Naruse Satoru , Thomas Philip J. , Muallem Shmuel
Published: April 2006

The SLC26 transporters are a family of mostly luminal Cl− and HCO3− transporters. The transport mechanism and the Cl−/HCO3− stoichiometry are not known for any member of the family. To address these questions, we simultaneously measured the HCO3− and Cl− fluxes and the current or membrane potential of slc26a3 and slc26a6 expressed in Xenopus laevis oocytes and the current of the transporters expressed in human embryonic kidney 293 cells. slc26a3 mediates a coupled 2Cl−/1HCO3− exchanger. The membrane potential modulated the apparent affinity for extracellular Cl− of Cl−/HCO3− exchange by slc26a3. Interestingly, the replacement of Cl− with NO3− or SCN− uncoupled the transport, with large NO3− and SCN− currents and low HCO3− transport. An apparent uncoupled current was also developed during the incubation of slc26a3-expressing oocytes in HCO3−-buffered Cl−-free media. These findings were used to develop a turnover cycle for Cl− and HCO3− transport by slc26a3. Cl− and HCO3− flux measurements revealed that slc26a6 mediates a 1Cl−/2HCO3− exchange. Accordingly, holding the membrane potential at 40 and −100 mV accelerated and inhibited, respectively, Cl−-mediated HCO3− influx, and holding the membrane potential at −100 mV increased HCO3−-mediated Cl− influx. These findings indicate that slc26a6 functions as a coupled 1Cl−/2HCO3− exchanger. The significance of isoform-specific Cl− and HCO3− transport stoichiometry by slc26a3 and slc26a6 is discussed in the context of diseases of epithelial Cl− absorption and HCO3− secretion.