bluuebunny/crossref_metadata_2025 huggingface dataset:
Observations of the behaviour of male eastern grey kangaroos when attacked by dingoes
Authors: Wright SM
Published: June 2005

Interactions between dingoes and male eastern grey kangaroos observed at Wallaby Creek (in northeastern
New South Wales) are described. Other than simple flight, large male kangaroos can react to
dingoes by defending themselves or fleeing to water. A male kangaroo defended himself during an
encounter lasting over 60min. His actions included high-standing, kicking, thumping the tail, and
hopping towards and watching the dingo. The encounter was made up of six intense bouts, during
which the dingo was within 5m of the kangaroo. Most bouts involved the dingo circling and the
kangaroo turning to face the dingo, with the kangaroo's degree of reaction depending on the distance
to the dingo. The response of the kangaroo diminished during later bouts. A second kangaroo fled
to water when pursued by a dingo and after swimming to shallow water lowered his body so only his
head showed. The dingo remained on the bank watching for some time. Both encounters ended with
the dingo leaving.
Distribution, habitat and satus of the Carpentarian rock-rat, Zyzomys palatalis
Authors: Churchill SK
Published: June 2005

A survey was conducted in the Northern Temtory and Queensland to determine the distribution, status and
habitat use of the recently described Carpentarian rock-rat, Zyzomys palatalis. The species was previously
known from two localities in the Gulf of Carpentaria, and this survey added only one new population to its
known range. The species is restricted to monsoon rainforest on scree slopes. In the Gulf region this habitat
is very limited and highly fragmented. The only areas where suitable habitat exists are in relatively
inaccessible gorges where permanent springs provide enough moisture to maintain the monsoon rainforests.
These patches of relict vegetation may be threatened by feral animals and changing fire regimes.
Because of the low population size of Z. palatalis and the small size of suitable habitat available, the
species is considered to be critically endangered.
Long-distance movments of juvenile brushtail possums (Trichosurus vulpecula) on farmland, Hawkes Bay, New Zealand
Authors: Cowan PE , Brockie RE , Ward GD , Efford MG
Published: June 2005

Long-distance movements of juvenile male and female brushtail possums (Trichosurus vulpecula) at a
farmland site, Hawke's Bay, New Zealand, were studied by radio-tracking. About 20% of radio-tagged
possums dispersed more than 2 km, moving up to 11.5 km from their natal area, most in a north-easterly
direction. The proportion of males that dispersed was higher than that of females, but the difference was not
statistically significant. All juveniles dispersing did so before they were one year old. The bimodal timing
of dispersal in summer and late winter to early spring reflected an underlying similar pattern of breeding.
Most possums made several moves before settling. A higher proportion of possums dispersed from the lowdensity
area of pastoral and cropping land than from the higher-density areas of swamp and willows. A few
dispersal records of ear-tagged animals were also obtained; most records were of males from the area of
pastoral and cropping land, and movements ranged from 3 to 25 km.
Plant coexistence depends on ecosystem nutrient cycles: Extension of the resource-ratio theory
Authors: Daufresne Tanguy , Hedin Lars O.
Published: June 2005

We present a model of plant-nutrient interactions that extends classical resource competition theory to environments in which essential nutrients (resources) are recycled between plant and soil pools and dissolved nutrients are lost through plant-available (i.e., inorganic forms) or plant-unavailable (i.e., complex organic forms) pathways. Losses by dissolved organic pathways can alter ratios of nutrients that are recycled and supplied within the plant-soil system, thereby influencing competition and coexistence among plant species. In special cases, our extended model does not differ from classical models, but in more realistic cases our model introduces new dynamical behavior that influences competitive outcomes. At equilibrium, coexistence still depends on nutrient supply and consumption, but nutrient supply includes recycling and is highly sensitive to whether a species promotes more organic losses of the nutrient that limits its own growth than of nutrients that limit its competitors. Because recycling operates with a time delay compared with consumption, recycling-mediated effects on competition can, under certain conditions, lead to sustained population oscillations. Our findings have implications for how we understand nutrient competition, nutrient cycles, and plant evolutionary strategies.
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: An anticancer agent targeting hypoxic cells
Authors: Seow Helen A. , Penketh Philip G. , Shyam Krishnamurthy , Rockwell Sara , Sartorelli Alan C.
Published: June 2005

To target malignant cells residing in hypoxic regions of solid tumors, we have designed and synthesized prodrugs generating the cytotoxic alkylating species 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) after bioreductive activation. We postulate that one of these agents, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119), requires enzymatic nitro reduction to produce 90CE, whereas another agent, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(4-nitrobenzyloxy)carbonyl]hydrazine (PNBC), can also be activated by nucleophilic attack by thiols such as glutathione (GSH)/GST. We demonstrated that these agents selectively kill hypoxic EMT6 mouse mammary carcinoma and CHO cells. In hypoxia, 50 μM KS119 produced 5 logs of kill of EMT6 cells without discernable cytotoxicity in air; similar effects were observed with CHO cells. PNBC was less efficacious against hypoxic tumor cells and also had some toxicity to aerobic cells, presumably because of GST/thiol activation, making PNBC less interesting as a selective hypoxic-cell cytotoxin. BALB/c mice with established EMT6 solid tumors were used to demonstrate that KS119 could reach and kill hypoxic cells in solid tumors. To gain information on bioreductive enzymes involved in the activation of KS119, cytotoxicity was measured in CHO cell lines overexpressing NADH:cytochrome
b
5 reductase (NBR), NADPH:cytochrome P450 reductase (NPR), or NAD(P)H: quinone oxidoreductase 1 (NQO1). Increased cytotoxicity occurred in cells overexpressing NBR and NPR, whereas overexpressed NQO1 had no effect. These findings were supported by enzymatic studies using purified NPR and xanthine oxidase to activate KS119. KS119 has significant potential as a hypoxia-selective tumor-cell cytotoxin and is unlikely to cause major toxicity to well oxygenated normal tissues.
Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na
V
1.9 to sensory transmission and nociceptive behavior
Authors: Priest Birgit T. , Murphy Beth A. , Lindia Jill A. , Diaz Carmen , Abbadie Catherine , Ritter Amy M. , Liberator Paul , Iyer Leslie M. , Kash Shera F. , Kohler Martin G. , Kaczorowski Gregory J. , MacIntyre D. Euan , Martin William J.
Published: June 2005

The transmission of pain signals after injury or inflammation depends in part on increased excitability of primary sensory neurons. Nociceptive neurons express multiple subtypes of voltage-gated sodium channels (Na
V
1s), each of which possesses unique features that may influence primary afferent excitability. Here, we examined the contribution of Na
V
1.9 to nociceptive signaling by studying the electrophysiological and behavioral phenotypes of mice with a disruption of the
SCN11A
gene, which encodes Na
V
1.9. Our results confirm that Na
V
1.9 underlies the persistent tetrodotoxin-resistant current in small-diameter dorsal root ganglion neurons but suggest that this current contributes little to mechanical thermal responsiveness in the absence of injury or to mechanical hypersensitivity after nerve injury or inflammation. However, the expression of Na
V
1.9 contributes to the persistent thermal hypersensitivity and spontaneous pain behavior after peripheral inflammation. These results suggest that inflammatory mediators modify the function of Na
V
1.9 to maintain inflammation-induced hyperalgesia.
Mountain gorilla tug-of-war: Silverbacks have limited control over reproduction in multimale groups
Authors: Bradley Brenda J. , Robbins Martha M. , Williamson Elizabeth A. , Steklis H. Dieter , Steklis Netzin Gerald , Eckhardt Nadin , Boesch Christophe , Vigilant Linda
Published: June 2005

To determine who fathers the offspring in wild mountain gorilla groups containing more than one adult male silverback, we genotyped nearly one-fourth (n= 92) of the mountain gorillas (Gorilla beringei beringei) living in the Virunga Volcanoes region of Africa. Paternity analysis of 48 offspring born into four groups between 1985 and 1999 revealed that, although all infants were sired by within-group males, the socially dominant silverback did not always monopolize reproduction within his group. Instead, the second-ranking male sired an average of 15% of group offspring. This result, in combination with previous findings that second-ranking males fare best by not leaving the group but by staying and waiting to assume dominance even if no reproduction is possible while waiting, is not consistent with expectations from a reproductive skew model in which the silverback concedes controllable reproduction to the second-ranking male. Instead, the data suggest a “tug-of-war” scenario in which neither the dominant nor the second-ranking male has full control over his relative reproductive share. The two top-ranked males were typically unrelated and this, in combination with the mixed paternity of group offspring, means that multimale gorilla groups do not approximate family groups. Instead, as long-term assemblages of related and unrelated individuals, gorilla groups are similar to chimpanzee groups and so offer interesting possibilities for kin-biased interactions among individuals.
The
Plasmodium falciparum
cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif
Authors: Pandey Kailash C. , Wang Stephanie X. , Sijwali Puran S. , Lau Anthony L. , McKerrow James H. , Rosenthal Philip J.
Published: June 2005

Falcipain-2 (FP2) is a papain family cysteine protease and important hemoglobinase of erythrocytic
Plasmodium falciparum
parasites. Inhibitors of FP2 block hemoglobin hydrolysis and parasite development, suggesting that this enzyme is a promising target for antimalarial chemotherapy. FP2 and related plasmodial cysteine proteases have an unusual 14-aa motif near the C terminus of the catalytic domain. Recent solution of the structure of FP2 showed this motif to form a β-hairpin that is distant from the enzyme active site and protrudes out from the protein. To evaluate the function of this motif, we compared the activity of the wild-type enzyme with that of a mutant lacking 10 aa of the motif (
Δ10
FP2).
Δ10
FP2 had nearly identical activity to that of the wild-type enzyme against peptide substrates and the protein substrates casein and gelatin. However,
Δ10
FP2 demonstrated negligible activity against hemoglobin or globin. FP2 that was inhibited with
trans
-epoxysuccinyl-
l
-leucylamido-(4-guanidino)butane (FP2
E-64
) formed a complex with hemoglobin, but
Δ10
FP2
E-64
did not, indicating that the motif mediates binding to hemoglobin independent of the active site. A peptide encoding the motif blocked hemoglobin hydrolysis, but not the hydrolysis of casein. Kinetics for the inhibition of
Δ10
FP2 were very similar to those for FP2 with peptidyl and protein inhibitors, but
Δ10
FP2 was poorly inhibited by the inhibitory prodomain of FP2. Our results indicate that FP2 utilizes an unusual motif for two specific functions, interaction with hemoglobin, its natural substrate, and interaction with the prodomain, its natural inhibitor.
α
1
-Adrenoceptor stimulation potentiates L-type Ca
2+
current through Ca
2+
/calmodulin-dependent PK II (CaMKII) activation in rat ventricular myocytes
Authors: O-Uchi Jin , Komukai Kimiaki , Kusakari Yoichiro , Obata Toru , Hongo Kenichi , Sasaki Hiroyuki , Kurihara Satoshi
Published: June 2005

α
1
-Adrenoceptor stimulation (α
1
ARS) modulates cardiac muscle contraction under physiological conditions by means of changes in Ca
2+
current through L-type channels (I
Ca,L
) and Ca
2+
ensitivity of the myofilaments. However, the cellular mechanisms of α
1
ARS are not fully clarified. In this study, we investigated the role of Ca
2+
/calmodulin-dependent PK II (CaMKII) in the regulation of I
Ca,L
during α
1
ARS in isolated adult rat ventricular myocytes by using the perforated patch–clamp technique. CaMKII inhibition with 0.5 μM KN-93 abolished the potentiation in I
Ca,L
observed during α
1
ARS by 10 μM phenylephrine. In the presence of PKC inhibitor (10 μM chelerythrine), the potentiation of I
Ca,L
by phenylephrine also disappeared. In Western immunoblotting analysis, phenylephrine (≥1 μM) increased the amount of autophosphorylated CaMKII (active CaMKII) significantly, and this increase was abolished by CaMKII inhibition or PKC inhibition. Also, we investigated changes in the subcellular localization of active CaMKII by using immunofluorescence microscopy and immunoelectron microscopy. Before α
1
ARS, active CaMKII was exclusively located just beneath the plasmalemma. However, after α
1
ARS, active CaMKII was localized close to transverse tubules, where most of L-type Ca
2+
channels are located. From these results, we propose that CaMKII, which exists near transverse tubules, is activated and phosphorylated by α
1
ARS and that CaMKII activation directly potentiates I
Ca,L
in rat ventricular myocytes.
Rapid evolutionary radiation of marine zooplankton in peripheral environments
Authors: Dawson Michael N , Hamner William M.
Published: June 2005

Populations of jellyfish,Mastigiassp., landlocked in tropical marine lakes during the Holocene, show extreme genetic isolation (0.74 ≤ φST≤ 1.00), founder effects (genetic diversity: 0.000 ≤ π ≤ 0.001), rapid morphological evolution, and behavioral adaptation. These results demonstrate incipient speciation in what we propose may be modern analogues of Plio-Pleistocene populations isolated in ocean basins by glacially lowered sea level and counterparts to modern marine populations isolated on archipelagos and other distant shores. Geographic isolation in novel environments, even if geologically brief, may contribute much to marine biodiversity because evolutionary rates in marine plankton can rival the most rapid speciation seen for limnetic species, such as cichlids and sticklebacks. Marine lakes present situations rare in their clarity for studying evolution in marine taxa.
Variable lymphocyte receptors in hagfish
Authors: Pancer Zeev , Saha Nil Ratan , Kasamatsu Jun , Suzuki Takashi , Amemiya Chris T. , Kasahara Masanori , Cooper Max D.
Published: June 2005

A previously uncharacterized type of variable lymphocyte receptors (VLR) was identified recently in the Sea lamprey. This jawless vertebrate generates an extensive VLR repertoire through differential insertion of neighboring diverse leucine-rich repeat (LRR) cassettes into an incomplete germ-lineVLRgene. We report here VLR homologs from two additional lamprey species and the presence of two types ofVLRgenes in hagfish, the only other order of contemporary jawless vertebrates. As in the Sea lamprey, the incomplete hagfish germ-lineVLR-Aand-Bgenes are modified in lymphocyte-like cells to generate highly diverse repertoires of VLR-A and -B proteins via a presently undetermined mechanism. This jawless-fish mode of VLR diversification starkly contrasts with the rearrangement of Ig V(D)J gene segments used by all jawed vertebrates to produce diverse repertoires of T and B lymphocyte antigen receptors. The development of two very different strategies for receptor diversification at the dawn of vertebrate evolution ≈500 million years ago attests to the fitness value of a lymphocyte-based system of anticipatory immunity.
Bone status in an animal model of chronic sub-optimal nutrition: a morphometric, densitometric and mechanical study
Authors: Boyer Patricia M. , Compagnucci Gabriela E. , Olivera María I. , Bozzini Clarisa , Roig María C. , Compagnucci Cecilia V. , Alippi Rosa M.
Published: June 2005

In children, inappropriate eating habits can induce a disease known as nutritional dwarfing (ND). Due to the link between nutritional condition and bone growth, the effects induced by a 20 % reduction of food intake on bone competence were assessed in an animal model of ND. Bone status during catch-up growth was also analysed. Male Wistar rats were divided into control (C) and ND groups. C rats were fedad libitum. ND received 80 % of the diet consumed by C for 4 weeks (T4); thereafter, they were fedad libitumfor 8 weeks. Results, expressed as mean (sem) for NDv.C, were as follows. At T4, body weight (g) and length (cm) and femur weight (g) and length (mm) were 97·35 (sem 5·89)v.199·07 (sem 9·24), 16·91 (sem 0·41)v.20·26 (sem 0·31), 0·30 (sem 0·01)v.0·46 (sem 0·01) and 23·09 (sem 0·29)v.26·98 (sem 0·26), respectively (P<0·001); bone mineral content (g) and density (g/cm2) were 0·014 (sem 0·002)v.0·030 (sem 0·002) and 0·061 (sem 0·004)v.0·080 (sem 0·003), respectively (P<0·001); load-bearing capacity (N), yielding load (N) and elastic stiffness (N/mm) were 25·06 (sem 1·24)v.50·34 (sem 2·94), 23·72 (sem 1·02)v.46·97 (sem 1·75) and 65·98 (sem 4·42)v.115·07 (sem 3·85), respectively (P<0·001); cross-sectional area (mm2) and moment of inertia (mm4) were 2·86 (sem 0·19)v.4·54 (sem 0·17) and 1·27 (sem 0·08)v.3·03 (sem 0·16), respectively (P<0·001). Significant effects were not evident in material properties. Parameters assessed normalized during re-feeding. These results suggest that the impaired mechanical femur competence in ND rats could be due to an altered bone mass and architectural distribution rather than to intrinsic quality. Re-feeding caused a reversal of the effects of food restriction on growth and bone parameters in ND rats.
Maternal dietary 22: 6n-3 is more effective than 18: 3n-3 in increasing the 22: 6n-3 content in phospholipids of glial cells from neonatal rat brain
Authors: Bowen Raffick A. R. , Clandinin Michael T.
Published: June 2005

One of the debates in infant nutrition concerns whether dietary 18: 3n-3 (linolenic acid) can provide for the accretion of 22: 6n-3 (docosahexaenoic acid, DHA) in neonatal tissues. The objective of the present study was to determine whether low or high 18: 3n-3v.preformed 22: 6n-3 in the maternal diet enabled a similar 22: 6n-3 content in the phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) of glial cells from whole brain (cerebrum and cerebellum) of 2-week-old rat pups. At parturition, the dams were fed semi-purified diets containing either increasing amounts of 18: 3n-3 (18: 2n-6 to 18: 3n-3 fatty acid ratio of 7·8: 1, 4·4: 1 or 1: 1), preformed DHA, or preformed 20: 4n-6 (arachidonic acid)+DHA. During the first 2 weeks of life, the rat pups from the respective dams received only their dam's milk. The fatty acid composition of the pups' stomach contents (dam's milk) and phospholipids from glial cells were quantified. The 20: 4n-6 and 22: 6n-3 content in the stomach from rat pups at 2 weeks of age reflected the fatty acid composition of the dam's diet. The 20: 4n-6 content of PE and PS in the glial cells was unaffected by maternal diet treatments. Preformed 22: 6n-3 in the maternal diet increased the 22: 6n-3 content of glial cell PE and PS compared with maternal diets providing an 18: 2n-6 to 18: 3n-3 fatty acid ratio of 7·8: 1, 4·4: 1 or 1: 1 (P<0·0001). There was no significant difference in the 20: 4n-6 and 22: 6n-3 content of glial cell PC and PI among maternal diet treatments. It was concluded that maternal dietary 22: 6n-3 is more effective than low or high levels of maternal dietary 18: 3n-3 at increasing the 22: 6n-3 content in PE and PS of glial cells from the whole brain of rat pups at 2 weeks of age. The findings from the present study have important implications for human infants fed infant formulas that are devoid of 22: 6n-3.
The influence of erythrocyte folate and serum vitamin B12status on birth weight
Authors: Relton Caroline L. , Pearce Mark S. , Parker Louise
Published: June 2005

The extent to which maternal folate and vitamin B12modulate infant birth weight is unclear. The present study investigated mothers in early gestation (mean 11·5 (sd 5·8) weeks) and neonates, at delivery. Erythrocyte (RBC) folate (mothers:n683; neonates:n614) and vitamin B12(mothers:n534; neonates:n614) were measured. Data on smoking habits were available for 44 % of pregnancies (n443). The relationship between vitamin levels and birth weight standardized for gender and gestational age was investigated, using linear regression and adjusting for possible confounding variables (maternal age, parity). Results are presented as standardized regression coefficients (b). Increasing maternal age was associated with elevated RBC folate (b0·11 (95 % CI 0·08, 0·15),P<0·001;n674) and smoking was associated with a decrease in maternal RBC folate (b−1·38 (95 % CI −1·92, −0·86),P=0·001;n319). Neonatal RBC folate was predicted by maternal RBC folate (b0·08 (95 % CI 0·04, 0·11),P=0·001;n315) and maternal vitamin B12(b0·08 (95 % CI 0·01, 0·16),P=0·02;n252). Smoking influenced maternal vitamin B12status (b−0·88 (95 % CI −1·49, −0·27),P=0·005;n231). Using univariate regression, smoking significantly influenced infant birth weight (b−2·15 (95 % CI −3·24, −1·04),P<0·001;n437). However, the effect of smoking on birth weight was statistically non-significant when considered in a multivariate regression model, leaving maternal RBC folate as the only significant predictor of birth weight (b0·25 (95 % CI 0·08, 0·42),P=0·005;n145). These findings suggest that maternal folate status is an important determinant of infant birth weight. The combined effects of smoking and reduced RBC status on birth weight require further investigation.
Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids
Authors: Jeong Yu-Jin , Choi Yean-Jung , Kwon Hyang-Mi , Kang Sang-Wook , Park Hyoung-Sook , Lee Myungsook , Kang Young-Hee
Published: June 2005

High plasma level of cholesterol is a well-known risk factor for atherosclerotic diseases. Oxidized LDL induces cellular and nuclear damage that leads to apoptotic cell death. We tested the hypothesis that flavonoids may function as antioxidants with regard to LDL incubated with 5 μm-Cu2+alone or in combination with human umbilical vein endothelial cells (HUVEC). Cytotoxicity and formation of thiobarbituric acid-reactive substances induced by Cu2+-oxidized LDL were examined in the presence of various subtypes of flavonoid. Flavanols, flavonols and flavanones at a non-toxic dose of 50 μm markedly inhibited LDL oxidation by inhibiting the formation of peroxidative products. In contrast, the flavones luteolin and apigenin had no such effect, with >30 % of cells killed after exposure to 0.1 mg LDL/ml. Protective flavonoids, especially (−)-epigallocatechin gallate, quercetin, rutin and hesperetin, inhibited HUVEC nuclear condensation and fragmentation induced by Cu2+-oxidized LDL. In addition, immunochemical staining and Western blot analysis revealed that anti-apoptotic Bcl-2 expression was enhanced following treatment with these protective flavonoids. However, Bax expression and caspase-3 cleavage stimulated by 18 h incubation with oxidized LDL were reduced following treatment with these protective flavonoids. The down-regulation of Bcl-2 and up-regulation of caspase-3 activation were reversed by the cytoprotective flavonoids, (−)-epigallocatechin gallate, quercetin and hesperetin, at ≥10 μm. These results suggest that flavonoids may differentially prevent Cu2+-oxidized LDL-induced apoptosis and promote cell survival as potent antioxidants. Survival potentials of certain flavonoids against cytotoxic oxidized LDL appeared to stem from their disparate chemical structure. Furthermore, dietary flavonoids may have therapeutic potential for protecting the endothelium from oxidative stress and oxidized LDL-triggered atherogenesis.
Effects of l-carnitine supplementation on milk production, litter gains and back-fat thickness in sows with a low energy and protein intake during lactation
Authors: Ramanau A. , Kluge H. , Eder K.
Published: June 2005

The present study investigated the effect of l-carnitine supplementation during pregnancy (125 mg/d) and lactation (250 mg/d) on milk production, litter gains and back-fat thickness in sows fed a low-energy and low-protein diet during lactation. Sows supplemented with l-carnitine produced more milk on days 11 and 18 of lactation (+18 %;P<0·05) and had higher litter gains during suckling (+20 %;P<0·01) than control sows. Loss of body weight during lactation was similar in both groups, but sows supplemented with l-carnitine had a greater reduction of back-fat thickness (+45 %;P<0·05) during lactation than control sows. In conclusion, this study shows that l-carnitine increases milk production and litter gains in sows in a strongly negative energy and N balance, and enhances body fat mobilisation.
Pregnancy increases urinary loss of carnitine and reduces plasma carnitine in Korean women
Authors: Cho Sang-Woon , Cha Youn-Soo
Published: June 2005

This study compared plasma and urinary carnitine concentrations in pregnant and non-pregnant Korean women. The subjects were fifty pregnant women and thirty non-pregnant women aged 24–28 years. During the first trimester, dietary carnitine intakes in the pregnant women were much lower than in non-pregnant women (70·00 (sd 29·22) μmol/d), but over the course of pregnancy carnitine intake increased from 44·64 (sd 24·84) μmol/d during the first trimester to 96·11 (sd 36·56) μmol/d during the third trimester. Pregnant women had a significantly lower plasma carnitine concentration than non-pregnant women. Plasma concentrations of non-esterified carnitine, acid-soluble acylcarnitine and total carnitine were significantly lower during the second and third trimesters than the first. Plasma acid-insoluble acylcarnitine levels, which tended to be higher in the non-pregnant women compared with the pregnant women, increased significantly as gestation proceeded. The urinary excretion of non-esterified carnitine, acid-soluble acylcarnitine and total carnitine was significantly higher in the pregnant women during the first and second trimesters than in non-pregnant women and decreased significantly as gestation proceeded. We found that there was a significant decrease in plasma carnitine level even though dietary carnitine intake increased as gestation proceeded. The low urinary excretion of carnitine in late pregnancy may be caused by an increased demand during pregnancy.
Brussels sprouts, inulin and fermented milk alter the faecal microbiota of human microbiota-associated rats as shown by PCR-temporal temperature gradient gel electrophoresis using universal,Lactobacillus and Bifidobacterium16S rRNA gene primers
Authors: Humblot Christèle , Bruneau Aurélia , Sutren Malène , Lhoste Evelyne F. , Doré Joël , Andrieux Claude , Rabot Sylvie
Published: June 2005

We investigated the effect of Brussels sprouts, inulin and a fermented milk on the faecal microbiota diversity of human microbiota-associated (HMA) rats by PCR-temporal temperature gradient gel electrophoresis (PCR-TTGE) using universal and group-specific 16S rRNA gene primers. The HMA rats were submitted to a control diet for 10 d (initial time), then switched to the experimental diets for 4 weeks (final time). Using universal primers, the mean degree of similarity between all faecal samples at initial time was 80·8 %. In the group consuming the control diet throughout the experiment, the mean degree of similarity between the PCR-TTGE profiles at initialv.final time was 76·8 %, reflecting a spontaneous temporal variation. The mean degree of similarity between control and experimental groups at final time was lower, 72·4 %, 74·4 % and 75·6 % for inulin, Brussels sprouts and fermented milk, respectively, indicating a dietary effect on the predominant populations. Using specific primers, bifidobacteria could be detected only in those rats that had consumed inulin, showing a specific increasing effect of this dietary compound. TheLactobacilluspopulation was very heterogeneous at initial time but tended to homogenize within each dietary group. At final time, caecal contents were collected for analysis of SCFA and β-glucuronidase activity. Inulin and Brussels sprouts increased the butyrate and acetate proportion, respectively, while the fermented milk did not modify the caecal biochemistry. This experiment shows for the first time that cruciferous vegetables are able to alter the diversity and the metabolic activities of the digestive microbiota in HMA rats.
Reduced adiposity in bitter melon (Momordica charantia) fed rats is associated with lower tissue triglyceride and higher plasma catecholamines
Authors: Chen Qixuan , Li Edmund T. S.
Published: June 2005

Slower weight gain and less visceral fat had been observed when rats fed a high-fat diet were supplemented with freeze-dried bitter melon (BM) juice; the metabolic consequences and possible mechanism(s) were further explored in the present study. In a 4-week experiment, rats were fed a low-fat (70 g/kg) or a high-fat (300 g/kg) diet with or without BM (7·5 g/kg or 0·75%). BM-supplemented rats had lower energy efficiency, visceral fat mass, plasma glucose and hepatic triacylglycerol, but higher serum free fatty acids and plasma catecholamines. In the second experiment, 7-week BM supplementation in high-fat diet rats led to a lowering of hepatic triacylglycerol (P<0·05) and steatosis score (P<0·05) similar to those in rats fed a low-fat diet. BM supplementation did not affect serum and hepatic cholesterol. However, plasma epinephrine and serum free fatty acid concentrations were increased (P<0·05). In the third experiment, BM(7·5 and 15 g/kg) and 1·5 % BM lowered triacylglycerol concentration in red gastrocnemius and tibialis anterior (P<0·05) muscle, but a dose–response effect was not observed. These data suggest that chronic BM feeding leads to a general decrease in tissue fat accumulation and that such an effect is mediated in part by enhanced sympathetic activity and lipolysis. BM or its bioactive ingredient(s) could be used as a dietary adjunct in the control of body weight and blood glucose.
Age and gender differences in children's food preferences
Authors: Cooke Lucy J. , Wardle Jane
Published: June 2005

The present study was conducted to examine the developmental patterning of food preferences in a large sample of British schoolchildren and to investigate possible gender differences. Using a cross-sectional survey design, the study was carried out in three primary and three secondary schools in West London, UK. A total of 1291 children aged from 4 to 16 years completed a 115-item food preference questionnaire in class time, supervised by class teachers and assistants. Children indicated whether they had ever tried each item and, if so, how much they liked it. We observed age-related increases in the number of foods tried (P<0·001), liked (P<0·005) and disliked (P<0·05). Controlling for the number of foods tried rendered the increase in dislikes non-significant and reversed the age effect on the number liked. Girls liked fruit (P<0·05) and vegetables (P<0·001) more than boys did; boys liked fatty and sugary foods (P<0·005), meat (P<0·001), processed meat products (P<0·001) and eggs (P<0·05) more than girls did. Some age differences were apparent in liking for categories of food, although the effects were not linear. Across ages and genders, children rated fatty and sugary foods most highly, although ratings for fruit were also high. Children's food preferences overall are not consistent with a healthy diet. Interventions should focus on increasing the familiarity, availability and accessibility of healthy foods and should be mindful of the need to target messages appropriately for boys who have less healthful food preferences than girls at all ages.
Comparison of two statistical approaches to predict all-cause mortality by dietary patterns in German elderly subjects
Authors: Hoffmann Kurt , Boeing Heiner , Boffetta Paolo , Nagel Gabriele , Orfanos Philippos , Ferrari Pietro , Bamia Christina
Published: June 2005

Dietary patterns are comprehensive variables of dietary intake appropriate to model the complex exposure in nutritional research. The objectives of this study were to identify dietary patterns by applying two statistical methods, principal component analysis (PCA) and reduced rank regression (RRR), and to assess their ability to predict all-cause mortality. Motivated by previous studies we chose percentages of energy from different macronutrients as response variables in the RRR analysis. We used data from 9356 German elderly subject enrolled in the European Prospective Investigation into Cancer and Nutrition study. The first RRR pattern, subjects which explained 30·8 % of variation in energy sources and especially much variation in intake of saturated fat, monounsaturated fat and carbohydrates was a significant predictor of all-cause mortality. The pattern score had high positive loadings in all types of meat, butter, sauces and eggs, and was inversely associated with bread and fruits. After adjustment for other known risk factors, the relative risks from the lowest to highest quintiles of the first RRR pattern score were 1·0, 1·01, 0·96, 1·32, 1·61 (P for trend: 0·0004). In contrast, the first two PCA patterns explaining 19·7 % of food intake variation but only 7·0 % of variation in energy sources were not related to mortality. These results suggest that variation in macronutrients is meaningful for mortality and that the RRR method is more appropriate than the classic PCA method to identify dietary patterns relevant to mortality.
Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects
Authors: Brighenti Furio , Valtueña Silvia , Pellegrini Nicoletta , Ardigò Diego , Del Rio Daniele , Salvatore Sara , Piatti PierMarco , Serafini Mauro , Zavaroni Ivana
Published: June 2005

Inflammation, a risk factor for cardiovascular disease, is associated with low plasma levels of antioxidant vitamins. In addition to vitamins, other antioxidants modulate the synthesis of inflammatory markers in vitro and contribute to the total antioxidant capacity (TAC) of a diet. However, the relationship between dietary TAC and markers of inflammation has never been evaluated in vivo. We investigated the relationship between dietary TAC and markers of systemic (high-sensitivity C-reactive protein (hs-CRP), leucocytes) and vascular (soluble intercellular cell adhesion molecule-1) inflammation in 243 non-diabetic subjects. General Linear Model (GLM) analysis showed a significant (P=0·005) inverse relationship between hs-CRP and quartiles of energy-adjusted dietary TAC, even when recognized modulating factors of inflammation, namely alcohol, fibre, vitamin C, α-tocopherol, β-carotene, BMI, waist circumference, HDL-cholesterol, hypertension, insulin sensitivity and plasma β-carotene, were included in the model as covariates (P=0·004). The relationship was stronger for subjects with hypertension (P=0·013 v. P=0·109 for normotensive individuals). Among dietary factors, TAC was significantly higher (5·3 (sd 3·0) v. 4·9 (sd 2·7) mmol Trolox/d; P=0·026) in subjects with low plasma hs-CRP (range: 0·0–4·1 mg/l) than in subjects with high plasma hs-CRP (range: 4·2–27·8 mg/l). We conclude that dietary TAC is inversely and independently correlated with plasma concentrations of hs-CRP and this could be one of the mechanisms explaining the protective effects against CVD of antioxidant-rich foods such as fruits, whole cereals and red wine. This could be of particular significance for subjects with high blood pressure.
The effects of drinks made from simple sugars on blood pressure in healthy older people
Authors: Visvanathan R. , Chen R. , Garcia M. , Horowitz M. , Chapman I.
Published: June 2005

The objective of the research was to determine the blood pressure (BP) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a randomised, cross-over study with ten (six females) healthy older subjects (mean age 72·20 (sem 1·50) years). BP, heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes (300 ml) of water and carbohydrate drinks with varying nutrient content (glucose, sucrose and fructose). A significant decline in BP over the first 60 min was seen following glucose (systolic BP (SBP) P<0·01, diastolic BP (DBP) P<0·01, mean arterial BP (MAP) P=0·03) and sucrose (SBP P<0·01, DBP P<0·01, MAP P<0·01) ingestion, although the decrease occurred earlier after glucose than sucrose ingestion (SBP 7·33 (sem 2·19) v. 21·00 (sem 4·30) min (P=0·03) and MAP 11·22 (sem 3·10) v. 17·00 (sem 3·78) min (P=0·03)). BP increased after water ingestion (SBP P=0·04, DBP P=0·18, MAP P=0·02) but did not change after fructose ingestion (SBP P=0·36, DBP P=0·81, MAP P=0·34). Post hoc analyses revealed that the BP (SBP, DBP and MAP) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion. Sucrose, which is used widely (table sugar), reduces BP as much as glucose. In contrast to this, fructose ingestion causes no change in BP. Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postprandial hypotension.
Diabetes-prone BioBreeding rats do not have a normal immune response when weaned to a diet containing fermentable fibre
Authors: Stillie RoseMarie , Bell Rhonda C. , Field Catherine J.
Published: June 2005

Diet is known to modulate the development of diabetes in diabetes-prone BioBreeding (BBdp) rats. The objective of the present study was to determine the effect of fermentable fibre (FF) on immune function in BBdp and diabetes-resistant BioBreeding (BBdr) rats after weaning. Weanling BBdp (thirty-six to thirty-eight per diet) and BBdr rats (thirty to thirty-two per diet) were fed a nutritionally complete, semi-purified, casein-based diet containing either cellulose (control diet, 8 % w/w) or FF (3·2 % cellulose+4·8 % w/w inulin). At 35 d, the small intestine was excised and lymphocytes isolated from spleen, mesenteric lymph nodes and Peyer's patches. Feeding FF to both BBdr and BBdp rats affected the production of anti-inflammatory cytokines (P=0·02). In BBdr rats, feeding FF compared with cellulose resulted in an increased small intestinal length (P=0·0031), higher proliferative (stimulation) index from both splenocytes (P=0·001) and mesenteric lymph nodes (P=0·04), and an increased proportion of CD8+ T-cells in the Peyer's patches (P=0·003). We did not observe an effect of diet on the number of IgA-bearing cells in the jejunum from BBdr rats. Feeding FF to BBdp rats did not affect the same parameters. BBdp rats had both a higher proportion of B-cells in the Peyer's patches (P=0·01) and a higher number of IgA+ cells in the jejunum (P=0·0036) when fed a diet containing FF, a response not observed in BBdr rats. We demonstrate that several aspects of the BBdp immune system respond differently than that of BBdr rats when challenged at weaning with FF.
Acute effects of meal fatty acids on postprandial NEFA, glucose and apo E response: implications for insulin sensitivity and lipoprotein regulation?
Authors: Jackson Kim G. , Wolstencroft Emma J. , Bateman Paul A. , Yaqoob Parveen , Williams Christine M.
Published: June 2005

Our aim was to determine whether meal fatty acids influence insulin and glucose responses to mixed meals and whether these effects can be explained by variations in postprandial NEFA and Apo, which regulate the metabolism of triacylglycerol-rich lipoproteins (Apo C and E). A single-blind crossover study examined the effects of single meals enriched in saturated fatty acids SFA),n-6 PUFA and MUFA on plasma metabolite and insulin responses. The triacylglycerol response following the PUFA meal showed a lower net incremental area under the curve than following the SFA and MUFA meals (P<0·007). Compared with the SFA meal, the PUFA meal showed a lower net incremental area under the curve for the NEFA response from initial suppression to the end of the postprandial period (180–480 min;P<0·02), and both PUFA and MUFA showed a lower net incremental glucose response (P<0·02), although insulin concentrations were similar between meals. The pattern of the Apo E response was also different following the SFA meal (P<0·02). There was a significant association between the net incremental NEFA (180–480 min) and glucose response (rs=0·409,P=0·025), and in multiple regression analysis the NEFA response accounted for 24 % of the variation in glucose response. Meal SFA have adverse effects on the postprandial glucose response that may be due to greater elevations in NEFA arising from differences in the metabolism of SFA-v.PUFA- and MUFA-rich lipoproteins. Elevated Apo E responses to high-SFA meals may have important implications for the hepatic metabolism of triacylglycerol-rich lipoproteins.
The effects of vitamin E supplementation on autoimmune-prone New Zealand black × New Zealand white F1 mice fed an oxidised oil diet
Authors: Hsieh Chia-Chien , Lin Bi-Fong
Published: June 2005

The purpose of the present study was to investigate the effect of vitamin E supplementation on autoimmune disease in New Zealand black×New Zealand white F1(NZB/W F1) female mice fed an oxidised oil diet. First, 5-month-old mice were fed an AIN-76 diet containing either 150 g fresh soyabean oil/kg (15S), 50 g fresh soyabean oil/kg + 100 g oxidised frying oil/kg (5S10F) or 5S10F supplemented with all-rac-α-tocopheryl acetate at 275 mg/kg diet level (5S10F5E) or 550 mg/kg (5S10F10E), respectively, in experiment 1. The results showed that mice fed the 5S10F10E diet had a lower anti-double-stranded DNA IgG antibody level and a longer lifespan than those fed the 15S and 5S10F diets. Therefore, the 5S10F and 5S10F10E treatments were repeated in experiment 2 for further analysis. The results showed that vitamin E supplementation in the oxidised oil significantly decreased thiobarbituric acid-reactive substance values in the kidney and spleen of NZB/W F1mice. Interferon-γ and IL-6 production by mitogen-stimulated splenocytes decreased in mice fed the 5S10F10E diet, whereas the secretion of IL-2 and IL-10 was not affected. The percentage of T-cells was significantly higher and that of MHC class II-bearing cells was lower in the spleens of the 5S10F10E group. The 5S10F10E group had a significantly higher linoleic acid (18: 2n-6) composition than the 5S10F diet group. Therefore, vitamin E supplementation in oxidised oil might decrease oxidative stress, anti-double-stranded DNA IgG antibody, regulate cytokines and lymphocyte subsets, and subsequently alleviate the severity of autoimmune disease such as systemic lupus erythematosus under oxidative stress.
The management of short-term intestinal failure in obese patients
Authors: Powell-Tuck Jeremy
Published: June 2005

The prevalence of obesity in the general population is high and it is inevitable that artificial feeding will be needed from time to time in the obese patient, particularly in the critical care setting. Against a background of generous endogenous stores of energy as adipose tissue and the ability of obese individuals to survive starvation longer than non-obese individuals, emphasis is placed on preserving lean body mass and optimizing physiological function. Insulin resistance is typical of the obese individual and is exacerbated by stress; overfeeding is dangerous, particularly if it results in hyperglycaemia. Refeeding syndrome also has to be avoided. Weight may be difficult to measure and lean body mass difficult to assess. Calculation of energy requirements is therefore problematic in practice in the obese individual and there is substantial evidence from controlled clinical trials of the safety of feeding at or below resting energy expenditure. If this approach is taken it is wise to provide a more generous than normal protein intake and to beware of patients with a very high baseline urinary N excretion.
Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease
Authors: Loots Gabriela G. , Kneissel Michaela , Keller Hansjoerg , Baptist Myma , Chang Jessie , Collette Nicole M. , Ovcharenko Dmitriy , Plajzer-Frick Ingrid , Rubin Edward M.
Published: June 2005

Mutations in distant regulatory elements can have a negative impact on human development and health, yet because of the difficulty of detecting these critical sequences, we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem (VB) disease, a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis, we characterized the expression of human sclerostin (SOST) from normal (SOSTwt) or Van Buchem (SOSTvbΔ) alleles. Only theSOSTwtallele faithfully expressed high levels of humanSOSTin the adult bone and had an impact on bone metabolism, consistent with the model that the VB noncoding deletion removes aSOST-specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays, we were able to identify a candidate enhancer element that drives humanSOSTexpression in osteoblast-like cell lines in vitro and in the skeletal anlage of the embryonic day 14.5 (E14.5) mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.
Distribution and intensity of constraint in mammalian genomic sequence
Authors: Cooper Gregory M. , Stone Eric A. , Asimenos George , Green Eric D. , Batzoglou Serafim , Sidow Arend
Published: June 2005

Comparisons of orthologous genomic DNA sequences can be used to characterize regions that have been subject to purifying selection and are enriched for functional elements. We here present the results of such an analysis on an alignment of sequences from 29 mammalian species. The alignment captures ∼3.9 neutral substitutions per site and spans ∼1.9 Mbp of the human genome. We identify constrained elements from 3 bp to over 1 kbp in length, covering ∼5.5% of the human locus. Our estimate for the total amount of nonexonic constraint experienced by this locus is roughly twice that for exonic constraint. Constrained elements tend to cluster, and we identify large constrained regions that correspond well with known functional elements. While constraint density inversely correlates with mobile element density, we also show the presence of unambiguously constrained elements overlapping mammalian ancestral repeats. In addition, we describe a number of elements in this region that have undergone intense purifying selection throughout mammalian evolution, and we show that these important elements are more numerous than previously thought. These results were obtained with Genomic Evolutionary Rate Profiling (GERP), a statistically rigorous and biologically transparent framework for constrained element identification. GERP identifies regions at high resolution that exhibit nucleotide substitution deficits, and measures these deficits as “rejected substitutions.” Rejected substitutions reflect the intensity of past purifying selection and are used to rank and characterize constrained elements. We anticipate that GERP and the types of analyses it facilitates will provide further insights and improved annotation for the human genome as mammalian genome sequence data become richer.