bluuebunny/crossref_metadata_2025 huggingface dataset:
Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats
Authors: El Mohsen Manal Abd , Marks Joanne , Kuhnle Gunter , Moore Kevin , Debnam Edward , Srai S. Kaila , Rice-Evans Catherine , Spencer Jeremy P. E.
Published: January 2006

Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore,p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18h after ingestion. At 2h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0·5 and 0·15nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18% after 2h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1·2% only 18h post-gavage, with the urine and faecal content constituting almost 90% of the total recovered pelargonidin.
Effect of dietary supplementation with βcasein A1 or A2 on markers of disease development in individuals at high risk of cardiovascular disease
Authors: Chin-Dusting Jaye , Shennan Jane , Jones Emma , Williams Carolyn , Kingwell Bronwyn , Dart Anthony
Published: January 2006

The present study is the first to examine the hypothesis that dietary supplementation with β-casein A1 promotes an increased risk relative to supplementation with β-casein A2 in patients traditionally at high risk of developing CVD. The study was conducted in fifteen asymptomatic participants (six male; nine female) at high risk of developing CVD. A double-blind cross-over study design was used with a total duration of 24 weeks. Dietary intervention was a daily supplementation (25g) of either casein A1 or A2 (for 12 weeks each). Surrogate measures of cardioprotection studied included the examination of vascular (endothelium and arterial) function, resting blood pressure, plasma lipids and biochemical markers of inflammation. Total plasma cholesterol levels were significantly lower following 12 weeks of both casein A1 and A2 interventions but the decrease was not different between intervention. Plasma insulin, homocysteine, C-reactive protein, fibrinogen, protein C and S and von Willebrand factor levels were not different between the two casein supplements. Endothelium function, measured as a vascular response using venous occlusion plethysmography to intra-aterial infusions of the endothelium-dependent agonist acetylcholine, were not different between the two casein interventions. Similarly, neither blood pressure nor measures of large artery stiffness were affected by differing the casein variant. We therefore conclude that there is no evidence from the present study that supplementation with casein A1 has any cardiovascular health disadvantage over consumption of casein A2.
A newly constructed and validated isoflavone database for the assessment of total genistein and daidzein intake
Authors: Ritchie Margaret R. , Cummings John H. , Morton Michael S. , Steel C. Michael , Bolton-Smith Caroline , Riches Andrew C.
Published: January 2006

The principal phyto-oestrogens (PO) in food are isoflavones, lignans, coumestans and prenylated flavonoids, with isoflavones and lignans being the most commonly found in UK diets. Until recently obtaining accurate data on the PO content of foods was hampered by lack of suitable analytical methods and validation techniques. Furthermore, although PO data exist for some foods, these foods may not be available in the UK. The aim of the present study was to construct a new, comprehensive isoflavone (total genistein + daidzein) database. Using data, mainly from recent GC–MS analysis, for approximately 300 foods available in the UK, and extensive recipe calculations, a new database was constructed containing approximately 6000 foods allocated an isoflavone value. By analysing 7d weighed food diaries, the database was subsequently used to estimate isoflavone intake in two groups of healthy volunteers, omnivores (n9) and vegetarians (n10). Mean isoflavone intake in the vegetarian and omnivorous group was 7·4 (sem 3·05) and 1·2 (sem 0·43) mg/d, respectively. Mean intake for the total group was 4·5 (sem 1·89) mg/d. Main food sources of isoflavones for the vegetarian group were soya milk (plain), meat-substitute foods containing textured vegetable protein and soya protein isolate, soya mince, wholemeal bread and rolls, white bread and rolls, croissants and pitta breads, beans, raisins and soya sauce. Main food sources of isoflavones for the omnivorous group were soya yogurts, wholemeal bread and rolls, white bread and rolls, garlic bread, nan bread and brown bread, sultanas and scones.
Processing of complementary food does not increase hair zinc levels and growth of infants in Kilosa district, rural Tanzania
Authors: Lachat Carl K. , Van Camp John H. , Mamiro Peter S. , Wayua Francis Obuoro , Opsomer Anne S. , Roberfroid Dominique A. , Kolsteren Patrick W.
Published: January 2006

A community-based, randomized, placebo-controlled, double-blind trial was conducted from March 2001 to March 2002 in Kilosa, a rural district of Morogoro Region in Tanzania. One hundred and fifty-eight infants were selected randomly from lists of local Maternal and Child Health Care Centres and received either processed complementary food (PCF) or unprocessed complementary food (UPCF) from age 6 to 12 months. Processing increased Zn solubility and energy density of the porridge prepared from the complementary food (CF) as determined in vitro. Phytate:Zn molar ratio of the PCF and UPCF was 25·8 and 47·5, respectively. Under the study conditions, the processing of CF did not improve Zn status as measured by hair analysis. No significant correlations were found between hair Zn values and anthropometric measurements. Our findings suggest that processing alone of cereal-based CF may be insufficient to ensure an adequate supply of Zn to improve growth and Zn status of infants. Dietary modification to tackle Zn deficiencies in similar target groups may therefore only be successful when other Zn-rich foods such as meat and fish are included.
Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in the gastrointestinal tract of suckling rats
Authors: Linderoth Ann , Prykhod'ko Olena , Ahrén Bo , Fåk Frida , Pierzynowski Stefan G. , Weström Björn R.
Published: January 2006

Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14d old, were fed a single dose of PHA (0·05mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3d after treatment. Initially, at 1–24h, the PHA bound along the gut mucosal lining, resulting in disturbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3d, the PHA binding had declined, and an uptake by enterocytes was observed. An increase in crypt cell proliferation and gut growth became evident during this period, together with a functional maturation, as indicated by increases in disaccharidase (maltase and sucrase) activities and the low macromolecular absorption capacity. Pancreas growth also increased, as did its content of digestive enzymes. We conclude that enteral exposure to PHA in suckling rats temporarily causes mucosal disarrangement and functional impediment of the gut, which may be explained by binding to and disruption of the gut mucosa and a two-fold increase in the plasma corticosterone concentration. These findings may lead to a better understanding of the role of diet in gastrointestinal maturation and may constitute a basis for the treatment of mammals having an immature gut.
Folate absorption from folate-fortified and processed foods using a human ileostomy model
Authors: Witthöft Cornelia M. , Arkbåge Karin , Johansson Madelene , Lundin Eva , Berglund Gerd , Zhang Jie-Xian , Lennernäs Hans , Dainty Jack R.
Published: January 2006

Data on folate absorption from food from validated human studies using physiological folate doses are still needed to estimate dietary requirements and to formulate recommendations. The aim of the present work was to study the effects from fortified and processed foods on folate absorption in ileostomy volunteers (n 9) using the area under the plasma concentration curve (AUC) and kinetic modelling. Using a standardized single-dose protocol, dairy products fortified with a candidate fortificant (6S)-5-methyltetrahydrofolate ((6S)-5-CH3-H4folate), folic acid-fortified bread and a dessert crème containing natural yeast folate polyglutamates were compared with folate supplements. Absorbed folate was estimated by AUC and a kinetic model, and non-absorbed folate by ileostomal folate excretion. Median apparent absorption from test foods ranged from 55 to 86%. Added folate-binding proteins (FBP) significantly reduced folate absorption from dairy products, as in the absence of FBP, AUC–dose-corrected ratios were increased and ileal folate excretion decreased. After in vivo gastrointestinal passage of dairy products containing FBP, up to 43% of the ingested FBP was found in ileostomal effluent. Folate absorption was similar for (6S)-5-CH3-H4folate fortificant from fermented milk and for folic acid from fortified bread. Folic acid, ingested as food fortificant in bread, was significantly less absorbed compared with an isolated supplement. We conclude that all tested foods were suitable matrices for folate fortification. However, dairy products, fortified with the new candidate fortificant (6S)-5-CH3-H4folate, are suitable if no active FBP is present.
Calpain Mediates a von Hippel-Lindau Protein–independent Destruction of Hypoxia-inducible Factor-1α
Authors: Zhou Jie , Köhl Roman , Herr Barbara , Frank Ronald , Brüne Bernhard
Published: January 2006

Hypoxia-inducible factor 1 (HIF-1) is controlled through stability regulation of its alpha subunit, which is expressed under hypoxia but degraded under normoxia. Degradation of HIF-1α requires association of the von Hippel Lindau protein (pVHL) to provoke ubiquitination followed by proteasomal digestion. Besides hypoxia, nitric oxide (NO) stabilizes HIF-1α under normoxia but destabilizes the protein under hypoxia. To understand the role of NO under hypoxia we made use of pVHL-deficient renal carcinoma cells (RCC4) that show a high steady state HIF-1α expression under normoxia. Exposing RCC4 cells to hypoxia in combination with the NO donor DETA-NO (2,2′-(hydroxynitrosohydrazono) bis-ethanimine), but not hypoxia or DETA-NO alone, decreased HIF-1α protein and attenuated HIF-1 transactivation. Mechanistically, we noticed a role of calpain because calpain inhibitors reversed HIF-1α degradation. Furthermore, chelating intracellular calcium attenuated HIF-1α destruction by hypoxia/DETA-NO, whereas a calcium increase was sufficient to lower the amount of HIF-1α even under normoxia. An active role of calpain in lowering HIF-1α amount was also evident in pVHL-containing human embryonic kidney cells when the calcium pump inhibitor thapsigargin reduced HIF-1α that was stabilized by the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). We conclude that calcium contributes to HIF-1α destruction involving the calpain system.
Rgf1p Is a Specific Rho1-GEF That Coordinates Cell Polarization with Cell Wall Biogenesis in Fission Yeast
Authors: García Patricia , Tajadura Virginia , García Ignacio , Sánchez Yolanda
Published: January 2006

Rho1p regulates cell integrity by controlling the actin cytoskeleton and cell wall synthesis. We have identified a new GEF, designated Rgf1p, which specifically regulates Rho1p during polarized growth. The phenotype of rgf1 null cells was very similar to that seen after depletion of Rho1p, 30% of cells being lysed. In addition, rgf1+deletion caused hypersensitivity to the antifungal drug Caspofungin and defects in the establishment of bipolar growth. rho1+, but none of the other GTPases of the Rho-family, suppressed the rgf1Δ phenotypes. Moreover, deletion of rgf1+suppressed the severe growth defect in rga1+null mutants (a Rho1-GAP, negative regulator). Rgf1p and Rho1p coimmunoprecipitated and overexpression of rgf1+specifically increased the GTP-bound Rho1p; it caused changes in cell morphology, and a large increase in β(1,3)-glucan synthase activity. These effects were similar to those elicited when the hyperactive rho1-G15V allele was expressed. A genetic relationship was observed between Rgf1p, Bgs4p (β[1,3]-glucan synthase), and Pck1p (protein kinase C [PKC] homologue); Bgs4p and Pck1p suppressed the hypersensitivity to Caspofungin in rgf1Δ mutants. Rgf1p localized to the growing ends and the septum, where Rho1, Pck1p, and Bgs4p are known to function. Our results suggest that Rgf1p probably activates the Rho functions necessary for coordinating actin deposition with cell wall biosynthesis during bipolar growth, allowing the cells to remodel their wall without risk of rupture.
Malarial parasites as geographical markers in migratory birds?
Authors: Fallon Sylvia M , Fleischer Robert C , Graves Gary R
Published: January 2006

We tested the hypothesis that malarial parasites (PlasmodiumandHaemoproteus) of black-throated blue warblers (Dendroica caerulescens) provide sufficient geographical signal to track population movements between the warbler's breeding and wintering habitats in North America. Our results from 1083 warblers sampled across the species' breeding range indicate that parasite lineages are geographically widespread and do not provide site-specific information. The wide distribution of malarial parasites probably reflects postnatal dispersal of their hosts as well as mixing of breeding populations on the wintering range. When compared to geographically structured parasites of sedentary Caribbean songbirds, patterns of malarial infections in black-throated blue warblers suggest that host–malaria dynamics of migratory and sedentary bird populations may be subject to contrasting selection pressures.
Ultraviolet reflectance by the cere of raptors
Authors: Mougeot François , Arroyo Beatriz E
Published: January 2006

Ultraviolet (UV) signals have been shown to play key roles in social and sexual signalling in birds. Using a spectrophotometer, we analysed the colour of the cere (skin above the beak) of a diurnal raptor, the Montagu's harrier (Circus pygargus), and show that it reflects in the UV part of the spectrum. The cere is a well-known sexual signal in raptors, with carotenoid based pigmentation being indicative of quality. We thus hypothesized that UV reflectance also signals quality. Accordingly, we found that in our sample of wild males, the location of the UV peak was related to the orangeness of cere and correlated with male body mass and condition (mass corrected for size). Also, males with brighter UV were mated to females that laid earlier, as expected if UV reflectance relates to a male's quality and attractiveness. Future studies should investigate the relationships between UV reflectance and carotenoid pigmentation of cere, and test how UV reflectance influences mate choice.
Hydrodynamic modelling of aquatic suction performance and intra-oral pressures: limitations for comparative studies
Authors: Van Wassenbergh Sam , Aerts Peter , Herrel Anthony
Published: January 2006

The magnitude of sub-ambient pressure inside the bucco-pharyngeal cavity of aquatic animals is generally considered a valuable metric of suction feeding performance. However, these pressures do not provide a direct indication of the effect of the suction act on the movement of the prey item. Especially when comparing suction performance of animals with differences in the shape of the expanding bucco-pharyngeal cavity, the link between speed of expansion, water velocity, force exerted on the prey and intra-oral pressure remains obscure. By using mathematical models of the heads of catfishes, a morphologically diverse group of aquatic suction feeders, these relationships were tested. The kinematics of these models were fine-tuned to transport a given prey towards the mouth in the same way. Next, the calculated pressures inside these models were compared. The results show that no simple relationship exists between the amount of generated sub-ambient pressure and the force exerted on the prey during suction feeding, unless animals of the same species are compared. Therefore, for evaluating suction performance in aquatic animals in future studies, the focus should be on the flow velocities in front of the mouth, for which a direct relationship exists with the hydrodynamic force exerted on prey.
Time-dependent solutions for particle-size segregation in shallow granular avalanches
Authors: Gray J.M.N.T , Shearer M , Thornton A.R
Published: January 2006

Rapid shallow granular free-surface flows develop in a wide range of industrial and geophysical flows, ranging from rotating kilns and blenders to rock-falls, snow slab-avalanches and debris-flows. Within these flows, grains of different sizes often separate out into inversely graded layers, with the large particles on top of the fines, by a process called kinetic sieving. In this paper, a recent theory is used to construct exact time-dependent two-dimensional solutions for the development of the particle-size distribution in inclined chute flows. The first problem assumes the flow is initially homogeneously mixed and is fed at the inflow with homogeneous material of the same concentration. Concentration shocks develop during the flow and the particles eventually separate out into inversely graded layers sufficiently far downstream. Sections with a monotonically decreasing shock height, between these layers, steepen and break in finite time. The second problem assumes that the material is normally graded, with the small particles on top of the coarse ones. In this case, shock waves, concentration expansions, non-centred expanding shock regions and breaking shocks develop. As the parameters are varied, nonlinearity leads to fundamental topological changes in the solution, and, in simple-shear, a logarithmic singularity prevents a steady-state solution from being attained.
On the macroscopic–mesoscopic mixture of a magnetorheological fluid
Authors: Chen Kuo-Ching
Published: January 2006

This paper is concerned with the modelling of a magnetorheological (MR) fluid in the presence of an applied magnetic field as a twofolded mixture—a macroscopic fluid continuum and mesoscopic multi-solid continua. By assigning to each solid particle a vectorial mesoscopic variable, which is defined as the nearest relative position vector with respect to other particles, the solid medium of the MR fluid is further treated as a mixture consisting of different components, specified by these mesoscopic variables. The treatment of multi-solid continua is similar to that in the mesoscopic theory of liquid crystals. However, the key difference lies in the fact that the time-discontinuity of the defined vectorial mesoscopic variable will give rise to a ‘pseudo’ chemical reaction in the solid continuum. The equation of the phenomenological mesoscopic distribution function of the solid continuum then has an additional production term from the pseudo chemical reaction, analogous to the collision term appearing in the Boltzmann equation. The mesoscopic and macroscopic balance equations are then derived and by assuming the special constitutive relations the macroscopic equation for the second moment of the distribution function can be obtained.
Binomial subsampling
Authors: Wiuf Carsten , Stumpf Michael P.H
Published: January 2006

In this paper, we discuss statistical familieswith the property that if the distribution of a random variableXis in, then so is the distribution ofZ∼Bi(X, p) for 0≤p≤1. (Here we takeZ∼Bi(X, p) to mean that givenX=x, Zis a draw from the binomial distribution Bi(x, p).) It is said that the family is closed under binomial subsampling. We characterize such families in terms of probability generating functions and for families with finite moments of all orders we give a necessary and sufficient condition for the family to be closed under binomial subsampling. The results are illustrated with power series and other examples, and related to examples from mathematical biology. Finally, some issues concerning inference are discussed.
An improved uniform approximation for diffraction integrals
Authors: Thompson Ian
Published: January 2006

A saddle point formula for integrals whose integrands possess a multi-valued exponent, and one or more poles is derived. The result includes a number of error (or Fresnel) functions, which is equal to the product of the number of poles and the number of sheets possessed by the exponent's Riemann surface. Such formulae have previously been suggested on the basis of known exact results and transformations, both of which are specific to a particular exponent. In general, the multi-valuedness can be taken into account by a straightforward modification to a standard procedure, which would ordinarily yield only a single error function for each pole. In the context of diffraction theory, this type of approximation remains valid in the vicinity of an optical boundary, even in some cases where a wavefield is incident in a direction almost or exactly parallel to a sharp obstacle (grazing incidence).
Empirical evidence for a nonlinear effect of galactic cosmic rays on clouds
Authors: Harrison R.Giles , Stephenson David B
Published: January 2006

Galactic cosmic ray (GCR) changes have been suggested to affect weather and climate, and new evidence is presented here directly linking GCRs with clouds. Clouds increase the diffuse solar radiation, measured continuously at UK surface meteorological sites since 1947. The ratio of diffuse to total solar radiation—the
diffuse fraction
(DF)—is used to infer cloud, and is compared with the daily mean neutron count rate measured at Climax, Colorado from 1951–2000, which provides a globally representative indicator of cosmic rays. Across the UK, on days of high cosmic ray flux (above 3600×10
2
 neutron counts h
−1
, which occur 87% of the time on average) compared with low cosmic ray flux, (i) the chance of an overcast day increases by (19±4) %, and (ii) the diffuse fraction increases by (2±0.3) %. During sudden transient reductions in cosmic rays (e.g. Forbush events), simultaneous decreases occur in the diffuse fraction. The diffuse radiation changes are, therefore, unambiguously due to cosmic rays. Although the statistically significant nonlinear cosmic ray effect is small, it will have a considerably larger aggregate effect on longer timescale (e.g. centennial) climate variations when day-to-day variability averages out.
Ecological divergence promotes the evolution of cryptic reproductive isolation
Authors: Nosil Patrik , Crespi Bernard J
Published: January 2006

Speciation can involve the evolution of ‘cryptic’ reproductive isolation that occurs after copulation but before hybrid offspring are produced. Because such cryptic barriers to gene exchange involve post-mating sexual interactions, analyses of their evolution have focused on sexual conflict or traditional sexual selection. Here, we show that ecological divergence between populations of herbivorous walking sticks is integral to the evolution of cryptic reproductive isolation. Low female fitness following between-population mating can reduce gene exchange between populations, thus acting as a form of cryptic isolation. Female walking sticks show reduced oviposition rate and lower lifetime fecundity following between-population versus within-population mating, but only for mating between populations using different host-plant species. Our results indicate that even inherently sexual forms of reproductive isolation can evolve as a by-product of ecological divergence and that post-mating sexual interactions do not necessarily evolve independently of the ecological environment.
The effects of floral mimics and models on each others' fitness
Authors: Anderson Bruce , Johnson Steven D
Published: January 2006

Plants that lack floral rewards may nevertheless attract pollinators by mimicking the flowers of rewarding plants. It has been suggested that both mimics and models should suffer reduced fitness when mimics are abundant relative to their models. By manipulating the relative densities of an orchid mimic
Disa nivea
and its rewarding model
Zaluzianskya microsiphon
in small experimental patches within a larger population we demonstrated that the mimic does indeed suffer reduced pollination success when locally common relative to its model. Behavioural experiments suggest that this phenomenon results from the tendency of the long-proboscid fly pollinator to avoid visits to neighbouring plants when encountering the mimic. No negative effect of the mimic on the pollination success of the model was detected. We propose that changes in pollinator flight behaviour, rather than pollinator conditioning, are likely to account for negative frequency-dependent reproductive success in deceptive orchids.
Alternative male reproductive tactics and the immunocompetence handicap in the Azorean rock-pool blenny,
Parablennius parvicornis
Authors: Ros Albert F.H , Bouton Niels , Santos Ricardo S , Oliveira Rui F
Published: January 2006

In the Azorean rock-pool blenny (
Parablennius parvicornis
) reproductively active males display alternative morphotypes, which differ in the expression of secondary sexual characters (SSC). Males expressing SSC, the M+ morphotype, have high androgen levels and compete for crevices that will be visited by females to spawn. M+ males holding nests court females and care for the eggs. Males with low expression of SSC, the M− morphotype, have low levels of androgens and reproduce by stealing fertilizations from the M+ males. Based on the hypothesis that androgens are immunosuppressive, we expected these morphotypes to differ in immunocompetence. To test this hypothesis, we conducted a field study in which we collected repeated blood samples to monitor leukocyte populations (blood smears), and to measure the primary antibody response of males that were experimentally challenged with a foreign non-pathogenic antigen (sheep red blood cells). Circulating levels of 11-ketotestosterone and testosterone were higher in M+ males than in M− males. Neither granulocyte nor thrombocyte counts did covariate with androgens or male tactic. In contrast, lymphocyte counts and humoral antibody response were negatively correlated with body size, and as expected, both were lower in M+ than in M− males. Interestingly, in M+ males androgen levels decreased after immunization, and this was less in nest-holder males than in M+ males that were floating around in the pools. Within each morphotype we found no relationship between androgens and immunocompetence. The latter result is not supportive for androgen regulated immunosuppression in M+ males. A possible alternative is enhancement of immunity in M− males. These males had relatively high levels of injuries in comparison with M+ males. High immunity might be a consequence of high infection rate because of such injuries.
Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on
Toxoplasma gondii
's ability to alter host behaviour
Authors: Webster J.P , Lamberton P.H.L , Donnelly C.A , Torrey E.F
Published: January 2006

With increasing pressure to understand transmissible agents, renewed recognition of infectious causation of both acute and chronic diseases is occurring. Epidemiological and neuropathological studies indicate that some cases of schizophrenia may be associated with environmental factors, such as exposure to the ubiquitous protozoan
Toxoplasma gondii
. Reasons for this include
T. gondii
's ability to establish persistent infection within the central nervous system, its ability to manipulate intermediate host behaviour, the occurrence of neurological and psychiatric symptoms in some infected individuals, and an association between infection with increased incidence of schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease have recently been demonstrated
in vitro
to possess anti-parasitic, and in particular anti-
T. gondii
, properties. Our aim here was thus to test the hypothesis that the anti-psychotic and mood stabilizing activity of some medications may be achieved, or at least augmented, through their
in vivo
inhibition of
T. gondii
replication and invasion in infected individuals. In particular we predicted, using the epidemiologically and clinically applicable rat-
T. gondii
model system, and following a previously described and neurologically characterized ‘feline attraction’ protocol that haloperidol (an anti-psychotic used in the treatment of mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer used in the treatment of mental illnesses including schizophrenia), would be, at least, as effective in preventing the development of
T. gondii
-associated behavioural and cognitive alterations as the standard anti-
T. gondii
chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while
T. gondii
appears to alter the rats’ perception of predation risk turning their innate aversion into a ‘suicidal’ feline attraction, anti-psychotic drugs prove as efficient as anti-
T. gondii
drugs in preventing such behavioural alterations. Our results have important implications regarding the aetiology and treatment of such disorders.
What's in it for me? Self-regard precludes altruism and spite in chimpanzees
Authors: Jensen Keith , Hare Brian , Call Josep , Tomasello Michael
Published: January 2006

Sensitivity to fairness may influence whether individuals choose to engage in acts that are mutually beneficial, selfish, altruistic, or spiteful. In a series of three experiments, chimpanzees (
Pan troglodytes
) could pull a rope to access out-of-reach food while concomitantly pulling another piece of food further away. In the first study, they could make a choice that solely benefited themselves (selfishness), or both themselves and another chimpanzee (mutualism). In the next two experiments, they could choose between providing food solely for another chimpanzee (altruism), or for neither while preventing the other chimpanzee from receiving a benefit (spite). The main result across all studies was that chimpanzees made their choices based solely on personal gain, with no regard for the outcomes of a conspecific. These results raise questions about the origins of human cooperative behaviour.
Experimental evidence that corticosterone affects offspring sex ratios in quail
Authors: Pike Thomas W , Petrie Marion
Published: January 2006

Recent studies have shown that some species of birds have a remarkable degree of control over the sex ratio of offspring they produce. However, the mechanism by which they achieve this feat is unknown. Hormones circulating in the breeding female are particularly sensitive to environmental perturbations, and so could provide a mechanism for her to bias the sex ratio of her offspring in favour of the sex that would derive greatest benefit from the prevailing environmental conditions. Here, we present details of an experiment in which we manipulated levels of testosterone, 17β-oestradiol and corticosterone in breeding female Japanese quail (
Coturnix coturnix japonica
) using Silastic implants and looked for effects on the sex ratio of offspring produced. Offspring sex ratio in this species was significantly correlated with faecal concentrations of the principal avian stress hormone, corticosterone, and artificially elevated levels of corticosterone resulted in significantly female-biased sex ratios at laying. Varying testosterone and 17β-oestradiol had no effect on sex ratio alone, and faecal levels of these hormones did not vary in response to corticosterone. Our results suggest that corticosterone may be part of the sex-biasing process in birds.
Environmental and management determinants of vegetation state on protected areas in the eastern Lowveld of South Africa
Authors: Peel M. J. S. , Kruger J. M. , Zacharias P. J. K.
Published: January 2006

Principal driving determinants (rainfall, geology, soil, tree density and canopy cover, animal numbers and feeding classes, and fire) of vegetation structure and function in the Lowveld savanna in South Africa were grouped for a 7‐year period to establish their influence on the limiting herbaceous layer. Grass type, abundance and cover were examined (450 sites; approximately 4000 km2). Using ordination, the variation and differences in the herbaceous‐response variables viz. perennial composition and cover allowed for the broad environmental grouping of areas of similar ecological potential. We demonstrate that areas of higher ecological potential carried higher densities of large herbivores without detrimentally affecting herbaceous composition and cover. The results have implications for land users and policy makers in terms of setting animal stocking density guidelines.
Erythroid differentiation denucleation factors (EDDFs) function as intrinsic, post‐erythropoietin regulators for mammalian erythroid terminal differentiation
Authors: Xue S.‐P. , Zhang S.‐F. , Ma W. , Zhang Z. , Liu P. , Zhao Q. , Han D.
Published: January 2006

Abstract.  Regulatory factors other than erythropoietin (Epo) dependence, that control mammalian erythroid terminal differentiation, are currently uncertain. Here we report the existence of erythroid differentiation factors in erythroid cytoplasm. Purification of these factors from cultured Friend virus anaemia (FVA)‐infected mouse splenic erythroblasts was carried out using isoelectrophoresis and high performance of liquid chromatograpy techniques. We have identified intracellular erythroid differentiation denucleation factors (EDDFs) that were able to mediate the events of post‐Epo‐dependent erythroblast terminal differentiation. Purified EDDF proteins bound specifically to the enhancer HS2 sequence of the globin gene activated the expression of haemoglobin in mouse erythroleukaemia and K562 erythroleukaemic cells and promoted them to differentiate into mature erythrocytes. EDDF proteins began to emerge at the pro‐early erythroblast stages upon exposure to Epo in culture, and increased dramatically in early erythroblast stage. The dynamic of EDDF expression and its action on the key events of erythroblast differentiation and denucleation appeared to be closely consistent with its spatiotemporal distribution. These results suggest that EDDFs are the critical intracellular regulatory factors that may act as the successive regulators to Epo, responsible for the final stages of erythroid terminal differentiation.
Virological analysis and phenotypic characterization of peripheral blood lymphocytes of hepatitis C virus-infected patients with and without mixed cryoglobulinaemia
Authors: Sansonno D , Lauletta G , Montrone M , Tucci F A , Nisi L , Dammacco F
Published: January 2006

In clinical and pathological terms hepatitis C virus (HCV)-infected patients can be subdivided into two main groups with and without mixed cryoglobulinaemia (MC). Involvement of blood mononuclear cells by HCV has potentially important implications. To this end, HCV-RNA levels in peripheral blood lymphocytes (PBL) preparations of 20 chronically HCV-infected patients with MC were measured and compared with those found in a group of 20 patients without MC matched for age, serum HCV-RNA, infectious genotype, source and presumable duration of infection. Phenotypic abnormalities of PBL subsets in each group of patients were determined by cell surface marker expression and compared. Results showed a significant enrichment of HCV-RNA in PBL of MC patients compared with a non-MC group (P = 0·01). Different distribution of HCV-RNA was accompanied by evidence of an increased frequency of circulating B cells. These data indicate that MC patients are characterized distinctly by a higher quota of cell-associated viral load.
Hyperglycaemia after glucose loading is a major predictor of preclinical atherosclerosis in nondiabetic subjects
Authors: Zhang Yi‐Fei , Hong Jie , Zhan Wei‐Wei , Li Xiao‐Ying , Gu Wei‐Qiong , Yang Yi‐Sheng , Xu Min , Ning Guang
Published: January 2006

Objective  Carotid intima–media thickness (IMT) has proved to be an independent marker of preclinical atherosclerosis. The aim of this study was to determine whether carotid IMT is associated with the plasma glucose concentration in the fasting state, after loading with oral glucose, or with the insulin sensitivity index (ISI) in nondiabetic subjects with different levels of glucose intolerance and insulin resistance.

Design  Cross‐sectional study.

Patients  A total of 160 nondiabetic subjects (147 from our obesity‐overweight clinic and 13 healthy normal subjects) were included in the present study, among them 33 had normal glucose tolerance (NGT), 13 had impaired fasting glucose (IFG), 80 had impaired glucose tolerance (IGT) and 34 had both IFG and IGT.

Measurements  Carotid IMT was assessed in the common carotid artery by a high‐resolution B‐mode ultrasound system. Plasma glucose was measured after fasting and at 30 min, 1, 2 and 3 h after a standard 75‐g load of glucose. The ISI was calculated from the frequent sampling intravenous glucose tolerance test (FSIGT).

Results  The IMT values in the NGT group were lower than those in the IFG, IGT and IFG + IGT groups (P < 0·03). No statistical difference in IMT values was found among the latter three groups. Univariate correlation analyses showed that the IMT was positively associated with age, plasma glucose concentrations 1 and 2 h after glucose loading, and serum concentration of low density lipoprotein (LDL) cholesterol (r = 0·39, 0·22, 0·25 and 0·18, respectively, P < 0·05). Multiple regression analysis showed that only age, plasma glucose concentration 2 h after glucose loading, and LDL cholesterol appeared to be significant correlates of the IMT (P < 0·0001), whereas the ISI was not.

Conclusions  In nondiabetic subjects with various degrees of glucose intolerance, there was a significant increase in IMT in those with IFG and IGT. Significant determinants of IMT, an indicator of preclinical atherosclerosis, include hyperglycaemia 2 h after a glucose load, age and LDL cholesterol, whereas fasting glucose concentration and the ISI were not significantly associated with IMT.
Genetic analyses in familial isolated hyperparathyroidism: implication for clinical assessment and surgical management
Authors: Cetani Filomena , Pardi Elena , Ambrogini Elena , Lemmi Monica , Borsari Simona , Cianferotti Luisella , Vignali Edda , Viacava Paolo , Berti Piero , Mariotti Stefano , Pinchera Aldo , Marcocci Claudio
Published: January 2006

Objective  Familial isolated primary hyperparathyroidism (FIPH) can result from either incomplete expression of a syndromic form of familial primary hyperparathyroidism [multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism–jaw tumour syndrome (HPT‐JT) or familial hypocalciuric hypercalcaemia (FHH)] or still unrecognized causes.

Design  Genetic analyses of MEN1, HRPT2 and CASR genes in FIHP.

Patients  Seven well‐characterized Italian kindreds with FIHP, with negative clinical features for MEN 1, HPT‐JT and FHH. The mean age (± SD) at diagnosis was 45 ± 17 years (range 18–70 years) in the probands and 42 ± 18 years (range 15–69 years) in the other affected subjects.

Measurements  Direct sequencing of germline DNA of the MEN1, HRPT2 and CASR genes from probands. The region of interest was amplified in some family members.

Results  Germline MEN1 mutations were detected in three kindreds. Multiglandular involvement was found in all but one affected subject belonging to the three kindreds with MEN1 mutations. In these patients persistence/relapse of the disease was observed unless an extensive parathyroidectomy (excision of 31/2 glands) had been performed, with the exception of one patient, who is currently normocalcaemic 168 months after excision of two glands. No mutations of MEN1, HRPT2 and CASR genes were identified in the remaining four families.

Conclusions  MEN1 genotyping appears worthwhile in FIHP families, as the finding of mutation(s) may predict multiglandular involvement and therefore have practical surgical implications, and prompt further investigation in the family, with the possibility of identifying new cases and beginning a programme of periodic surveillance for emergence of tumours in all carriers.
Increase of interferon‐γ‐inducible CXC chemokine CXCL10 serum levels in patients with active Graves’ disease, and modulation by methimazole therapy
Authors: Antonelli Alessandro , Rotondi Mario , Fallahi Poupak , Romagnani Paola , Ferrari Silvia Martina , Barani Lucio , Ferrannini Ele , Serio Mario
Published: January 2006

Background  CXCL10 plays an important role in the initial phases of Graves’ disease (GD) and autoimmune thyroiditis (AT); however, until now, CXCL10 serum levels (sCXCL10) in patients with GD have never been evaluated in relation to thyroid function and treatment.

Objective  To evaluate sCXCL10 in GD.

Design  Cross‐sectional.

Patients  One hundred and three GD, 164 AT, 20 nontoxic multinodular goitre (NTMNG), 16 toxic nodular goitre (TNG) patients and 70 healthy controls (age‐ and sex‐matched).

Measurements  We measured sCXCL10 in patients and controls, to relate this parameter to the clinical phenotype.

Results  Mean sCXCL10 in GD and AT patients were comparable (122 ± 81 and 133 ± 102 pg/ml) and significantly higher (P < 0·01) than in controls or NTMNG patients (73 ± 32 and 76 ± 25 pg/ml, respectively). Hyperthyroid GD had significantly higher sCXCL10 than euthyroid or hypothyroid GD (145 ± 92, 107 ± 56 and 105 ± 46 pg/ml, respectively; P = 0·01). GD patients with untreated hyperthyroidism had higher sCXCL10 than hyperthyroid or euthyroid GD patients under methimazole (MMI) treatment (166 ± 125, 124 ± 41 and 94 ± 35 pg/ml, respectively; P = 0·006). Comparable sCXCL10 levels were observed in newly diagnosed untreated hyperthyroid GD patients with respect to untreated patients with relapse of hyperthyroidism after a previous MMI course (176 ± 125, 155 ± 97 pg/ml, respectively). GD had similar sCXCL10 to AT and higher than TNG patients or controls (all age‐ and sex‐matched) (144 ± 81, 149 ± 114, 101 ± 27 and 86 ± 44 pg/ml, respectively; P = 0·02).

Conclusions  sCXCL10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. The reduction in sCXCL10 in treated patients with GD may be related to the immunomodulatory effects of MMI.
p53 immunostaining in lichen sclerosus is related to ischaemic stress and is not a marker of differentiated vulvar intraepithelial neoplasia (d‐VIN)
Authors: Liegl B , Regauer S
Published: January 2006

Aim : To analyse p53 immunoreactivity in 207 biopsy specimens of lichen sclerosus (LS) and ‘differentiated vulvar intraepithelial neoplasia’ (d‐VIN), a postulated precursor lesion for LS‐associated vulvar squamous cell carcinoma (SCC), which is characterized by atypical basal keratinocyte proliferations with p53+ basal/suprabasal keratinocyte nuclei.

Methods and results : Forty early, 78 classic, 30 hypertrophic vulvar LS, 26 paediatric vulvar and penile LS, 33 vulvar LS‐associated SCC and 30 vulvar/penile control specimens were examined for p53 expression and the presence of d‐VIN. Nuclear p53 staining was observed in 175/207 LS biopsy specimems. Eighty percent of early and 69% of paediatric LS showed discontinuous/continous p53 staining in basal keratinocytes. Classic LS showed no p53 staining in 17%, discontinuous basal keratinocyte staining in 20%, continuous basal keratinocyte staining in 58%, basal/suprabasal staining in 5%. Hypertrophic LS revealed basal keratinocyte staining in 32% and basal/suprabasal staining in 61%. p53 staining was associated with sclerosis of blood vessels and dermis, lymphoid infiltrates, vasculitis and hypertrophic LS. d‐VIN was seen in 2% of LS alone and in 24% of LS‐associated SCC.

Conclusion : d‐VIN in LS is rare, while p53 staining is common and best explained as an ischaemic stress response due to poor oxygenation, vasculitis and inflammation rather than as a marker of a precancerous lesion in LS.
Cell cycle regulators and apoptosis‐associated proteins in relation to proliferative activity and degree of apoptosis in HNPCC versus sporadic endometrial carcinoma
Authors: Rijcken F , van der Zee A , van der Sluis T , Boersma‐van Ek W , Kleibeuker J , Hollema H
Published: January 2006

Aims : Mismatch repair gene malfunction occurs early in the carcinogenesis of hereditary non‐polyposis colorectal cancers (HNPCCs), leading to an accelerated accumulation of mutations and possibly to change in expression of cell cycle proteins. There is strong evidence that tumorigenesis in HNPCCs differs from sporadic ones. HNPCC‐related endometrial cancers are less well studied. Our aim was to compare expression of cell cycle and apoptosis‐related proteins in relation to proliferation and apoptosis in HNPCC‐related and sporadic endometrial cancers to identify differences in their carcinogenetic pathways.

Methods and results : Eighteen HNPCC‐related endometrial cancers, each matched by tumour type, stage and grade with two sporadic endometrial cancers, were examined for proliferation, apoptosis and the expression of oestrogen and progesterone receptors, cyclin B1, D3 and E, p21, p27, bcl‐2, bax, p53 and COX‐2. No differences in proliferation or apoptotic indices were detected between HNPCC‐related and sporadic endometrial cancers. Cyclin B1 expression was significantly higher in HNPCC‐related cancers than in sporadic endometrial cancers. More HNPCC‐related endometrial cancers had total loss of bax expression.

Conclusions : Apart from differences in cyclin B1 and bax expression, HNPCC‐related and sporadic endometrial cancers are comparable. The subtle differences detected are consistent with the minor clinical diversity between HNPCC‐related and sporadic endometrial cancers.