bluuebunny/crossref_metadata_2025 huggingface dataset:
β-Catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development
Authors: Delmas Véronique , Beermann Friedrich , Martinozzi Silvia , Carreira Suzanne , Ackermann Julien , Kumasaka Mayuko , Denat Laurence , Goodall Jane , Luciani Flavie , Viros Amaya , Demirkan Nese , Bastian Boris C. , Goding Colin R. , Larue Lionel
Published: November 2007

Tumor progression is a multistep process in which proproliferation mutations must be accompanied by suppression of senescence. In melanoma, proproliferative signals are provided by activating mutations in NRAS and BRAF, whereas senescence is bypassed by inactivation of the p16Ink4a gene. Melanomas also frequently exhibit constitutive activation of the Wnt/β-catenin pathway that is presumed to induce proliferation, as it does in carcinomas. We show here that, contrary to expectations, stabilized β-catenin reduces the number of melanoblasts in vivo and immortalizes primary skin melanocytes by silencing the p16Ink4a promoter. Significantly, in a novel mouse model for melanoma, stabilized β-catenin bypasses the requirement for p16Ink4a mutations and, together with an activated N-Ras oncogene, leads to melanoma with high penetrance and short latency. The results reveal that synergy between the Wnt and mitogen-activated protein (MAP) kinase pathways may represent an important mechanism underpinning the genesis of melanoma, a highly aggressive and increasingly common disease.
Variation in haematozoan parasitism at local and landscape levels in the red‐billed quelea Quelea quelea
Authors: Durrant Kate L. , Reed Jennifer L. , Jones Peter J. , Dallimer Martin , Cheke Robert A. , McWilliam Andrew N. , Fleischer Robert C.
Published: November 2007

The red‐billed quelea Quelea quelea, one of the most abundant birds in the world, presents two fundamental conundrums that we investigate here with a novel approach using blood parasite assemblages at two spatial scales, landscape and individual. The quelea of southern Africa Q. q. lathamii are split by a hypothesized migratory divide, where birds follow rain fronts in one of two directions (NW or SE). This divide is not detectable in the host population using microsatellite data, and here we show that it is also not apparent from our large‐scale phylogeographical analyses of the haematozoan parasite. At a finer scale, the colourful and variable breeding plumage of male red‐billed quelea has not previously shown a correlation with predictors of quality, as it does in many other bird species. The male's breeding plumage is partially based on carotenoid colouration, the quality of which has been correlated with haematozoan infection in other bird species. However, we found no correlation between intensity of male carotenoid colouration and haematozoan infection. Our results do not contradict the hypothesis that male breeding plumage in this species serves to identify individuals rather than to indicate quality. Finally, we recovered the greatest number of haematozoan lineages from any phylogenetic survey of a single host species to date. Understanding the reasons for the extreme diversity of parasite lineages in this species may assist in explaining the success of the red‐billed quelea in anthropogenic landscapes.
Head ornaments in owls: what are their functions?
Authors: Galeotti Paolo , Rubolini Diego
Published: November 2007

We studied head ornamentation in owls by focussing on the hypothesis that it may serve both intra‐ and interspecific communication. We carried out pairwise comparisons of morphological, ecological and behavioural traits on a subset of closely related species with contrasting head ornamentation patterns. We found that the degree of head ornamentation was associated with habitat and activity rhythm, highly ornamented species (e.g., most of the genusBubo) living preferentially in open habitats and being active by day, but not with body size. Although our results do not exclude the possibility that head ornaments may represent a warning mechanism to startle predators and mobbers, they nevertheless suggest that such signals have evolved for visual communication with conspecifics, being more expressed in species that may use them more effectively without incurring the risk of predation or disturbance.
Expression level of beta protein 1 mRNA in Chinese breast cancer patients: A potential molecular marker for poor prognosis
Authors: Yu Man , Yang Yi , Shi Yurong , Wang Defa , Wei Xiyin , Zhang Ning , Niu Ruifang
Published: November 2007

Recent studies revealed high ectopic beta protein 1 (BP1) expression in breast cancer. Remarkably, up to 100% (18/18) of estrogen receptor (ER)‐negative tumors and 89% (25/28) of tumors from African American women were BP1‐positive. However, the role of BP1 in breast cancer development and its clinical significance still has not been well defined. In the present study, we analyzed the quantitative level of BP1 mRNA in breast carcinomas using real‐time polymerase chain reaction and aimed to elucidate its association with tumor characteristics and patient prognosis. Our data showed that BP1 mRNA was expressed at significantly higher levels in tumors with lymph node metastasis, with a high histological grade, and in those that were of ER‐negative status. Furthermore, overexpression of BP1 was significantly associated with poor outcome of patients harboring tumors with a high histological grade and negative ER. Using both in vitro and in vivo systems, we also showed that the transcript level of BP1 was positively correlated to the growth rate of breast tumor cells. Taken together, our results support the notion that BP1 might contribute to breast neoplastic transformation or tumor progression and suggest for the first time that BP1 mRNA level has potential as a prognostic predictor for breast cancer. (Cancer Sci 2008; 99: 173–178)
Dietary cation–anion difference and cadmium concentration in grasses fertilized with chloride
Authors: Pelletier S. , Simpson R. , Randall P. , Bélanger G. , Tremblay G. F. , Seguin P. , Drapeau R , Allard G.
Published: November 2007

High dietary cation–anion difference (DCAD) of grass herbage increases the occurrence of hypocalcaemia of dairy cows. Application of chloride fertilizer reduces DCAD of herbage but it could increase cadmium concentration in herbage. This study includes an experiment conducted in Australia and in Canada. A glasshouse experiment in Australia evaluated the effect of four rates of chloride application (0–240 kg ha−1) on values of herbage DCAD and cadmium concentration of above‐ground plant material of timothy (Phleum pratenseL.) and phalaris (Phalaris aquaticaL.), harvested 6 weeks after sowing and grown on two soils that had received cadmium either as a contaminant in superphosphate (soil + Super) or in sewage biosolids (soil + Bio) along with respective control soils (soil 0 Super and soil 0 Bio). Application of chloride fertilizer decreased values of herbage DCAD by 349 mmolc kg−1dry matter (DM). Herbage DCAD values were highest on the 0 Bio soil (739 mmolc kg−1  DM) and were not different among the three other soils. Species did not differ in herbage DCAD values. Cadmium concentration in the above‐ground plant material was highest on the +Bio soil treatment (1·67 mg kg−1DM) and was lower for the three other soil treatments. Above‐ground plant material of phalaris had a higher cadmium concentration than that of timothy. Application of chloride fertilizer did not affect cadmium concentration in above‐ground plant material, despite the high cadmium content of the soil on the +Bio treatment. The field experiment in Canada evaluated the effect of four rates of chloride application (0–144 kg ha−1) on cadmium concentration of a timothy‐based grass sward grown on four sites with soils of different potassium content. Application of chloride fertilizer increased cadmium concentration of herbage at two of the four sites but the maximum increase in cadmium concentration was only 0·025 mg kg−1DM. Chloride fertilizer can be applied to decrease forage DCAD with minimal risk of increasing Cd in the food chain.
Effect of livestock breed and grazing intensity on grazing systems: 5. Management and policy implications
Authors: Mills J. , Rook A. J. , Dumont B. , Isselstein J. , Scimone M. , Wallis De Vries M. F.
Published: November 2007

This paper explores the management and policy implications of research findings investigating the use of grazing intensity and traditional breeds to achieve biodiversity outcomes on grasslands in four countries of Europe. An economic analysis, based on these research findings, indicated that financial assistance and/or premium prices are required to achieve sustainable grazing systems with a high biodiversity. The research findings suggested that existing agri‐environment scheme prescriptions based only on blanket stocking rates are too crude to increase plant diversity, lacking consideration of initial site conditions. Conversely, some invertebrates seem to rapidly benefit from lenient stocking, highlighting the importance of clear goals for agri‐environment schemes. Recommendations for an appropriate support package to deliver grazing systems with high biodiversity are presented.
Crown rust affects plant performance and interference ability of Italian ryegrass in the post‐epidemic generation
Authors: Mattner S. W. , Parbery D. G.
Published: November 2007

This study investigated the effects of crown rust (caused by Puccinia coronata f.sp. lolii) in Italian ryegrass (Lolium multiflorum) on plant growth and interference ability in the post‐epidemic generation. Rust‐infected Italian ryegrass plants produced seeds with lower weights than healthy plants (on average proportionately 0·36 lower). Furthermore, the early seedling vigour of plants from rust‐infected parents was reduced by 0·50 compared with seed from healthy parents. Under disease‐free conditions in the post‐epidemic generation, mature plants from rust‐infected parents produced 0·13 less shoot dry weight, 0·15 fewer tillers, 0·11 fewer leaves and 0·25 less leaf area than plants from healthy parents. As such, the effects of crown rust in Italian ryegrass persisted for at least one post‐epidemic generation. Under rust‐infected conditions in the post‐epidemic generation, however, the difference in performance between plants from healthy and rust‐infected parents was minimal. This suggests that any advantage plants gain from having healthy parents, compared with rust‐infected parents, might be lost when the post‐epidemic generation is grown under conditions of rust infection. Irrespective of rust infection in the post‐epidemic generation, the magnitude of intra‐specific interference was greater in monocultures of Italian ryegrass from healthy parents than in those from rust‐infected parents. However, the magnitude of inter‐specific interference and the relative interference ability of plants of rust‐infected and healthy parents did not differ. The implications of these results to plant ecology are discussed.
Effects of residual dry matter on net primary production and plant functional groups in Californian annual grasslands
Authors: Bartolome J. W. , Jackson R. D. , Betts A. D. K. , Connor J. M. , Nader G. A. , Tate K. W.
Published: November 2007

A five‐year experiment tested the response of above‐ground net primary production (ANPP) and plant functional groups to manipulations in residual dry matter (RDM), reflecting typical grazing practices in Californian annual grasslands. The RDM treatments were 225, 560, 900 and 5000 kg ha−1 with the latter treatment representing no grazing by livestock. ANPP in autumn, winter and spring showed a strong year × RDM interaction indicating that, in periods with higher herbage mass, the highest RDM treatment, representative of no grazing, was usually more productive. However, the opposite pattern was observed for the autumn period when ANPP was lowest. Random effects models indicated that at most 0·20 of the variation in ANPP for any of the three seasons stemmed from RDM treatments, with the remaining variation partitioned among temporal and spatial dimensions or not explained. Cover of grass species was highest under the highest RDM treatment in four of the five years, and lowest for the lowest RDM treatment compared with the two intermediate RDM treatments in the two years with the highest herbage masses. Cover of forbs and clover was higher on the lowest RDM treatment and lower on the highest RDM treatment than on the intermediate treatments. The results suggest that residual RDM values above 550 kg RDM ha−1 are appropriate for annual grasslands with a mean annual precipitation of more than 400 mm and offer a compromise between herbage use and promotion of future productivity and diversity, but direct control of ANPP and composition via management is not attainable because the environmental factors are predominant.
Mixing whole‐crop pea–oat silage and grass–clover silage: positive effects on intake and milk production of dairy cows
Authors: Rondahl T. , Bertilsson J. , Martinsson K.
Published: November 2007

Forty‐eight high‐yielding dairy cows of the Swedish Red breed were used to examine the effects of providing pea–oat silage (P), grass–clover silage (G) and a 0·50:0·50 mixture of the silages (M) ad libitum in diets with two concentrate levels (7 or 10 kg d−1). A 9‐week experiment, including a 2‐week pre‐experimental period in which the cows were all fed the same diet, and an in vivo apparent digestibility study were conducted comparing the six dietary treatments (M7, M10, P7, P10, G7, G10). Intake and digestibility of the diets and milk production and live weight of the cows were measured. The G silage [11·3 MJ ME kg−1 dry matter (DM)] was first‐cut grass herbage wilted for 24 h prior to addition of an additive, containing formic acid, propionic acid and ammonia, at 4 L t−1 fresh matter (FM). The P forage was cut when the peas were at pod fill and ensiled directly with 6 L t−1 FM of the same additive. The main hypothesis tested, that cows fed the M silage would produce more milk than the cows fed either the P or the G silages, was confirmed. The cows fed the M7 dietary treatment had similar milk yield and milk composition to cows offered the M10, G10 and P10 dietary treatments, and cows offered the G7 and P7 dietary treatments had lower milk and milk protein yields. This suggested that a mixed ration of pea–oat bi‐crop and grass–clover silage has a concentrate‐sparing effect, and that the use of pea–oat bi‐crop and grass–clover silage as a mixed ration for high‐yielding dairy cows can be recommended.
Patterns of leaf and root regrowth, and allocation of water‐soluble carbohydrate reserves following defoliation of plants of prairie grass (Bromus willdenowii Kunth.)
Authors: Turner L. R. , Donaghy D. J. , Lane P. A. , Rawnsley R. P.
Published: November 2007

This study utilized leaf stage‐based defoliation intervals to describe the concentrations and contents of water‐soluble carbohydrate (WSC) and nitrogen (N) in stubble and root reserves and their effect on the regrowth of prairie grass (Bromus willdenowii Kunth.) plants. The priority sequence for allocation of WSC reserves during the regrowth period was also investigated. There were substantially higher concentrations of WSC and N in the stubble compared with the roots following defoliation, confirming the stubble as the primary site for energy storage, with roots playing a lesser role. However, high R2 values for the relationships between WSC concentration in roots and regrowth variables suggested that plants of prairie grass were reliant on WSC reserves from the roots in addition to the stubble to meet the energy requirements of plants until adequate photosynthetic tissue had been produced. The sequence of priority for allocation of WSC reserves followed the order of leaf growth, root growth and tillering during the regrowth period. Although WSC reserves were identified as the primary contributor to plant regrowth following defoliation, there was also a strong relationship between stubble N concentration and regrowth variables.
Influence of factor IX on overall plasma coagulability and fibrinolytic potential as measured by global assay: monitoring in haemophilia B
Authors: GOLDENBERG N. A. , BOMBARDIER C. , HATHAWAY W. E. , McFARLAND K. , JACOBSON L. , MANCO‐JOHNSON M. J.
Published: November 2007

Summary.  We sought to determine the influence of factor IX (FIX) deficiency upon overall coagulative and fibrinolytic capacities in plasma using the clot formation and lysis (CloFAL) assay, and to investigate the role of this global assay as an adjunctive monitoring tool in haemophilia B. CloFAL assay parameters were measured in vitro in platelet‐poor plasma in relation to FIX activity and antigen (FIX:Ag), and were determined ex vivo among FIX‐deficient patients (n = 41) in comparison to healthy individuals (n = 48). Supplementation of FIX‐deficient plasma with FIX in vitro demonstrated a non‐linear concentration dependence of FIX upon overall plasma coagulability. Ex vivo, coagulability was significantly decreased in FIX‐deficient vs. healthy subjects among adults [median coagulation index (CI): 4% vs. 104% respectively; P < 0.001] and children (median CI: 9% vs. 63%; P < 0.001). Fibrinolytic capacity was increased in adult FIX‐deficient vs. healthy subjects (median fibrinolytic index: 216% vs. 125%, respectively, P < 0.001), and was supported by a trend in shortened euglobulin lysis time (ELT). Severe haemophilia B patients showed heterogeneity in aberrant CloFAL assay waveforms, influenced partly by FIX:Ag levels. Patients with relatively preserved FIX:Ag (i.e. dysfunctional FIX) exhibited a shorter time to maximal amplitude in clot formation than those with type I deficiency. During patient treatment monitoring, markedly hypocoagulable CloFAL assay waveforms normalized following 100% correction with infused FIX. The CloFAL global assay detects FIX deficiency, demonstrates differences in coagulability between dysfunctional FIX and type I deficiency, and appears useful as an adjunctive test to routine FIX measurement in monitoring haemophilia B treatment.
Comparison of metastatic brain tumour models using three different methods: the morphological role of the pia mater
Authors: Saito Norihiko , Hatori Tsutomu , Murata Nozomu , Zhang Ze‐An , Nonaka Hiroko , Aoki Kazuya , Iwabuchi Satoshi , Ueda Morikazu
Published: November 2007

As methods of cancer diagnosis and treatment progress, interest in metastatic brain tumours continues to increase. There are many studies using various methods of animal model and we considered that each model reflects different pathological processes because of the unique composition of the brain. We prepared metastatic brain tumour models using three different methods. In this study, we attempted to elucidate the roles of the pia mater in brain metastasis. The metastatic foci showed an angiocentric pattern, forming collars of neoplastic cells, and were designated ‘perivascular proliferations’. Furthermore, we observed neoplastic cells that infiltrated the brain parenchyma, the border of which had become indistinct. These were labelled ‘invasive proliferations’. The internal carotid artery injection model reflects haematogenous metastasis. In this model, both perivascular and invasive proliferations were observed. The intrathecal injection model reflects leptomeningeal carcinomatosis. In this model, metastasis to the meninges was observed. In the stereotactic injection model, the tumour proliferation at the injection site and the infiltration into the brain parenchyma were observed. The pia‐glial membrane serves as a scaffold when neoplastic cells spread to the perivascular space forming angiocentric pattern. The pia‐glial membrane is found between the brain parenchyma and blood vessels. Blood vessels penetrate the brain through tunnels known as perivascular spaces that are covered by pia mater. Three different methods which we prepared reflect three different pathological processes. Our findings suggest that the pia mater is a critical factor in brain metastasis.
Central Neural and Endocrine Mechanisms of Non‐Exercise Activity Thermogenesis and Their Potential Impact on Obesity
Authors: Novak C. M. , Levine J. A.
Published: November 2007

The rise in obesity is associated with a decline in the amount of physical activity in which people engage. The energy expended through everyday non‐exercise activity, called non‐exercise activity thermogenesis (NEAT), has a considerable potential impact on energy balance and weight gain. Comparatively little attention has been paid to the central mechanisms of energy expenditure and how decreases in NEAT might contribute to obesity. In this review, we first examine the sensory and endocrine mechanisms through which energy availability and energy balance are detected that may influence NEAT. Second, we describe the neural pathways that integrate these signals. Lastly, we consider the effector mechanisms that modulate NEAT through the alteration of activity levels as well as through changes in the energy efficiency of movement. Systems that regulate NEAT according to energy balance may be linked to neural circuits that modulate sleep, addiction and the stress response. The neural and endocrine systems that control NEAT are potential targets for the treatment of obesity.
Reduced Expression of the KATP Channel Subunit, Kir6.2, is Associated with Decreased Expression of Neuropeptide Y and Agouti‐Related Protein in the Hypothalami of Zucker Diabetic Fatty Rats
Authors: Gyte A. , Pritchard L. E. , Jones H. B. , Brennand J. C. , White A.
Published: November 2007

The link between obesity and diabetes is not fully understood but there is evidence to suggest that hypothalamic signalling pathways may be involved. The hypothalamic neuropeptides, pro‐opiomelanocortin (POMC), neuropeptide Y (NPY) and agouti‐related protein (AGRP) are central to the regulation of food intake and have been implicated in glucose homeostasis. Therefore, the expression of these genes was quantified in hypothalami from diabetic Zucker fatty (ZDF) rats and nondiabetic Zucker fatty (ZF) rats at 6, 8, 10 and 14 weeks of age. Although both strains are obese, only ZDF rats develop pancreatic degeneration and diabetes over this time period. In both ZF and ZDF rats, POMC gene expression was decreased in obese versus lean rats at all ages. By contrast, although there was the expected increase in both NPY and AGRP expression in obese 14‐week‐old ZF rats, the expression of NPY and AGRP was decreased in 6‐week‐old obese ZDF rats with hyperinsulinaemia and in 14‐week‐old rats with the additional hyperglycaemia. Therefore, candidate genes involved in glucose, and insulin signalling pathways were examined in obese ZDF rats over this age range. We found that expression of the ATP‐sensitive potassium (KATP) channel component, Kir6.2, was decreased in obese ZDF rats and was lower compared to ZF rats in each age group tested. Furthermore, immunofluorescence analysis showed that Kir6.2 protein expression was reduced in the dorsomedial and ventromedial hypothalamic nuclei of 6‐week‐old prediabetic ZDF rats compared to ZF rats. The Kir6.2 immunofluorescence colocalised with NPY throughout the hypothalamus. The differences in Kir6.2 expression in ZF and ZDF rats mimic those of NPY and AGRP, which could infer that the changes occur in the same neurones. Overall, these data suggest that chronic changes in hypothalamic Kir6.2 expression may be associated with the development of hyperinsulinaemia and hyperglycaemia in ZDF rats.
Distribution of Galanin Receptor‐2 Immunoreactive Neurones in the Ovine Hypothalamus: No Evidence for Involvement in the Control of Gonadotrophin‐Releasing Hormone Secretion
Authors: Chambers G. , Whitelaw C. M. , Robinson J. E. , Evans N. P.
Published: November 2007

Galanin is a small neuropeptide that mediates its effects via three receptor isoforms: galanin receptor‐1, galanin receptor‐2 and galanin receptor‐3 (Gal‐R1, Gal‐R2 and Gal‐R3). Galanin is thought to be an important intermediate in signalling in the hypothalamic‐pituitary‐gonadal axis and has been widely detected in the ovine hypothalamus. The expression of galanin and Gal‐R1 has been reported to fluctuate during the reproductive cycle. Although the distribution of Gal‐R1 has been determined in the ovine hypothalamus, the distribution of Gal‐R2 was hitherto unknown. Using immunohistological and immunofluorescence techniques, we have mapped the distribution of Gal‐R2 in the ovine hypothalamus, collected during the follicular phase of the oestrous cycle and examined colocalisation of Gal‐R2 with oestrogen receptor alpha (ERα) and gonadotrophin‐releasing hormone (GnRH). Gal‐R2 was expressed in several regions of the hypothalamus (supraoptic nucleus, paraventricular nucleus, ventromedial nucleus, arcuate nucleus) but not as widely expressed as Gal‐R1. Areas of Gal‐R2 expression overlapped with those reported for Gal‐R1. We observed that, in certain defined regions of the hypothalamus, up to 50% of neurones that express Gal‐R2 also express ERα. No neurones coexpressed Gal‐R2 and GnRH. Thus, we conclude that, in follicular phase animals, this receptor plays little or no role in direct intermediary signal transmission in GnRH‐mediated control of the reproductive cycle.
Agonist Activity of the 3‐Hydroxy Metabolites of Tibolone Through the Oestrogen Receptor in the Mouse N20.1 Oligodendrocyte Cell Line and Normal Human Astrocytes
Authors: Guzmán C. B. , Zhao C. , Deighton‐Collins S. , Kleerekoper M. , Benjamins J. A. , Skafar D. F.
Published: November 2007

17β‐oestradiol (E2) may have a beneficial impact on the development of age‐related diseases, in part through α and β oestrogen receptors (ER) in glia. Tibolone, a synthetic steroid, could influence glial‐mediated neuroprotection if agonist oestrogenic activity is demonstrable. We used the N20.1 mouse oligodendrocyte cell line as a glial cell model to evaluate the response of ERα and ERβ through oestrogen‐response element (ERE) and AP‐1‐driven reporters to E2, 4‐hydroxytamoxifen (4OHT) and to two tibolone metabolites, 3α‐hydroxytibolone (3α‐OH‐Tib) and 3β‐hydroxytibolone (3β‐OH‐Tib). In addition, we tested the activity of these same ligands through the endogenous ERα in human normal astrocytes. Because endogenous ER was not detected in the N20.1 cells, we tested the ability of exogenous ER to activate transcription in response to ligands (100 nM) using a transient cotransfection assay with an ERα expression vector. To test the antagonist activity of 3α‐OH‐Tib and 3β‐OH‐Tib, we used them in combination with E2 (10−8 M), at concentrations of 10−7 M and 10−6 M. The human normal astrocytes were treated similarly, with the exception that no ER‐encoding DNA was used. Specific ER ligand mediated activity was shown using the E2 antagonist ICI 182 780 and the pSG5 empty vector. E2, 3α‐OH‐Tib, and 3β‐OH‐Tib stimulated ERα on an ERE‐promoter at each concentration (P < 0.001) but not at an AP‐1‐driven promoter. 4OHT was an effective antagonist, but did not exhibit agonist activity on the ERE‐driven promoter. 4OHT was an effective agonist through ERα on an AP‐1‐driven promoter. 3α‐OH‐Tib and 3β‐OH‐Tib were not effective antagonists of E2. Both metabolites acted through the ER because the addition of an E2 antagonist blocked their activity. These results show that 3α‐OH‐Tib and 3β‐OH‐Tib exert agonist activity, yet lack antagonist or additive activity, through the ERα and ERβ on an ERE‐driven but not on an AP‐1‐driven promoter in a glial cell model and in normal human astrocytes. This contrasts with the effects of 4OHT, which exerted little or no agonist activity, but reduced E2‐stimulated activity through ERα on the ERE, in the same cells.
The Transcriptome of the Rat Hypothalamic‐Neurohypophyseal System is Highly Strain‐Dependent
Authors: Hindmarch C. , Yao S. , Hesketh S. , Jessop D. , Harbuz M. , Paton J. , Murphy D.
Published: November 2007

We have used microarrays to comprehensively describe the transcriptomes of the supraoptic nucleus (SON), the paraventricular nucleus (PVN) and the neurointermediate lobe of adult male Sprague‐Dawley (SD) and Wistar‐Kyoto (WKY) rats, as well as the PVN of Wistar rats. Comparison of these gene lists has enabled us to identify surprisingly large differences in hypothalamic‐neurohypophyseal system gene expression patterns in these three strains. We have also shown that different transcript populations are enriched in the PVN and the SON of SD and WKY rats. The transcriptome differences catalogued here may be molecular substrates for the neuro‐humoral phenotypic differences exhibited by different strains of rats.
Cell‐specific SpoIIIE assembly and DNA translocation polarity are dictated by chromosome orientation
Authors: Becker Eric C. , Pogliano Kit
Published: November 2007

SpoIIIE and FtsK are related proteins that translocate chromosomes across septa. Previous results suggested that SpoIIIE exports DNA and that translocation polarity is governed by the cell‐specific regulation of its assembly, but that FtsK is a reversible motor for which translocation polarity is governed by its DNA substrate. Seeking to reconcile these conclusions, we used cell‐specific GFP tagging to demonstrate that SpoIIIE assembles a complex only in the mother cell, from which DNA is exported, but that DNA translocation‐defective SpoIIIE proteins assemble in both cells. Altering chromosome architecture by soj‐spo0J and racA soj‐spo0J mutations allowed wild‐type SpoIIIE to assemble in the forespore and export the forespore chromosome. Combining LacI‐CFP tagging of oriC with time‐lapse microscopy, we demonstrate that the chromosome is exported from the forespore when oriC fails to be trapped in the forespore. Thus, the position of oriC after septation determines which cell will receive the chromosome and which will assemble SpoIIIE.
RbrA, a cyanobacterial rubrerythrin, functions as a FNR‐dependent peroxidase in heterocysts in protection of nitrogenase from damage by hydrogen peroxide in Anabaena sp. PCC 7120
Authors: Zhao Weixing , Ye Zi , Zhao Jindong
Published: November 2007

The heterocyst is a specialized cell for nitrogen fixation in some filamentous cyanobacteria. Here we report that a rubrerythrin (RbrA) from Anabaena sp. PCC 7120 functions as a peroxidase in heterocysts and plays an important role in protection of nitrogenase. The electron donor for RbrA in H2O2 reduction is NADPH and the electron transfer from NADPH to RbrA depends on ferredoxin:NADP+ oxidoreductase. A rbrA mutant (r27) grew much more slowly than the wild type under diazotrophic conditions. Its nitrogenase activity measured in air was only 8% of that measured under anoxic conditions. Staining r27 filaments with 2′,7′‐dichlorodihydrofluorescein diacetate indicated that heterocysts had a higher H2O2 concentration than the vegetative cells. The expression of rbrA was controlled by two promoters and the promoter for the smaller transcript was regulated by HetR. Spatial expression of rbrA was studied and the results showed that the transcription is localized predominantly in heterocysts. In a mutant lacking nifH and rbrA, the H2O2 concentration in heterocysts was lower than that in the vegetative cells, suggesting that NifH is involved in H2O2 generation. Our results demonstrate that RbrA is a critical enzyme for H2O2 decomposition and provide evidence that nitrogenase autoprotection is important in heterocysts.
The SUN41 and SUN42 genes are essential for cell separation in Candida albicans
Authors: Firon Arnaud , Aubert Sylvie , Iraqui Ismaïl , Guadagnini Stéphanie , Goyard Sophie , Prévost Marie‐Christine , Janbon Guilhem , D'Enfert Christophe
Published: November 2007

Completion of the yeast cell cycle involves extensive remodelling of the cell wall upon separation of mother and daughter cells. We have studied two members of the ascomycete‐specific SUN gene family in Candida albicans. Inactivation of SUN41 yields defects in cell separation and hyphal elongation while inactivation of SUN42 results in minor phenotypic alterations. Simultaneous inactivation of SUN41 and SUN42 is synthetically lethal due to lysis of mother cells after septation. Electronic microscopy reveals cell wall defects mainly localized in the region surrounding the septa. This phenotype is osmoremediable and the conditional double mutants show increased sensitivity to cell wall or cell membrane perturbing agents. The essential function shared by Sun41p and Sun42p is conserved among yeasts because UTH1, a Saccharomyces cerevisiae SUN gene, suppresses the lethality of SUN41 and SUN42 conditional mutants. Investigation of functional genomic data obtained in S. cerevisiae reveals links between members of the SUN gene family and the RAM pathway regulating cell wall‐degrading enzymes specifically involved during cell separation. Thus, the main function of ascomycetous Sun proteins appears linked to cell wall remodelling, with a probable role in counter‐balancing cell wall degradation to avoid cell lysis upon cell separation.
Oesophageal tone and sensation in the transition zone between proximal striated and distal smooth muscle oesophagus
Authors: Karamanolis G. , Stevens W. , Vos R. , Tack J. , Clave P. , Sifrim D.
Published: November 2007

Abstract  Previous studies have shown that the proximal striated muscle oesophagus is less compliant and more sensitive than the distal smooth muscle oesophagus. Conventional and high resolution manometry described a transition zone between striated and smooth muscle oesophagus. We aimed to evaluate oesophageal tone and sensitivity at the transition zone of oesophagus in healthy volunteers. In 18 subjects (seven men, mean age: 28 years) an oesophageal barostat study was performed. Tone and sensitivity were assessed using stepwise isobaric distensions with the balloon located at transition zone and at distal oesophagus in random order. To study the effect induced on transition zone by a previous distension at the distal oesophagus and vice versa, identical protocol was repeated after 7 days with inverted order. Initial distension of a region is referred to as ‘naïf’ distension and distension of a region following the distension of the other segment as ‘primed’ distension. Assessment of three oesophageal symptoms (chest pain, heartburn and ‘other’) was obtained at the end of every distension step. Compliance was significantly higher in the transition zone than in the distal oesophagus (1.47 ± 0.14 vs 1.09 ± 0.09 mL mmHg−1, P = 0.03) after ‘naif’ distensions. This difference was not observed during ‘primed’ distensions. Higher sensitivity at transition zone level was found in 11/18 (61%) subjects compared to 6/18 (33%, P < 0.05) at smooth muscle oesophagus. Chest pain and ‘other’ symptom were more often induced by distention of the transition zone, whereas heartburn was equally triggered by distension of either region. The transition zone is more complaint and more sensitive than smooth muscle oesophagus.
Genetic analysis of the physiological responses to low boron stress in Arabidopsis thaliana
Authors: ZENG CHANGYING , HAN YANLAI , SHI LEI , PENG LISHUN , WANG YUNHUA , XU FANGSEN , MENG JINLING
Published: November 2007

Boron (B) is an essential micronutrient for higher plants. There is wide genetic variation in the response to B deficiency among plant species and cultivars. The objective of this study was to identify quantitative trait loci (QTL) that control B efficiency in natural Arabidopsis accessions. The B efficiency coefficient (BEC) and seed yield under low B conditions (SYLB) were investigated by solution culture in two separate experiments in an Arabidopsis recombinant inbred line (RIL) population. Both of the traits studied exhibited high transgressive variation in the RIL population, and, in total, five and three QTL were identified for BEC and SYLB, respectively. Three of the five QTL, including the QTL, AtBE1‐2, that has a large effect on the BEC, were found at the interval of the corresponding QTL for SYLB in both experiments. The close genetic relationship between BEC and SYLB was further confirmed by conditional QTL mapping in the RIL population and unconditional QTL mapping in an AtBE1‐2‐segregated F2 population. Epistatic interactions for the tested traits were analysed, and were found to be widespread in the detected QTL of Arabidopsis in the RIL population. Comparison of the QTL interval for B efficiency with reported B‐related genes showed that 10 B‐related genes, together with one BOR1 homolog (BOR5, At1g74810) were located in the QTL region of AtBE1‐2. These results suggest that natural variation in B efficiency in Arabidopsis has a complex molecular basis. They also provide a basis for fine mapping and cloning of the B‐efficiency genes, with the ultimate aim of discovering the physiological mechanism of action of the genes.
Interaction of heavy metals with the sulphur metabolism in angiosperms from an ecological point of view
Authors: ERNST WILFRIED H. O. , KRAUSS GERD‐JOACHIM , VERKLEIJ JOS A. C. , WESENBERG DIRK
Published: November 2007

The metabolism of sulphur in angiosperms is reviewed under the aspect of exposure to ecologically relevant concentrations of sulphur, heavy metals and metalloids. Because of the inconsistent use of the term ‘metal tolerance’, in this review the degree of tolerance to arsenic and heavy metals is divided into three categories: hypotolerance, basal tolerance and hypertolerance.

The composition of nutrient solutions applied to physiological experiments let see that the well‐known interactions of calcium, sulphate and zinc supply with uptake of heavy metals, especially cadmium are insufficiently considered. Expression of genes involved in reductive sulphate assimilation pathway and enzyme activities are stimulated by cadmium and partially by copper, but nearly not by other heavy metals. The synthesis of the sulphur‐rich compounds glucosinolates, metallothioneins and phytochelatins is affected in a metal‐specific way. Phytochelatin levels are low in all metal(loid)‐hypertolerant plant species growing in the natural environment on metal(loid)‐enriched soils.

If laboratory experiments mimic the natural environments, especially high Zn/Cd ratios and good sulphur supply, and chemical analyses are extended to more mineral elements than the single metal(loid) under investigation, a better understanding of the impact of metal(loid)s on the sulphur metabolism can be achieved.
Haplotype‐specific sequence‐based typing shows the novel allele HLA‐A*030105
Authors: Albis‐Camps M. , Blasczyk R. , Horn P. A.
Published: November 2007

The novel allele human leukocyte antigen (HLA)‐A*030105 differs from HLA‐A*030101 by a synonymous nucleotide exchange at codon 87 in exon 2 (G→A).
Identification of a novel HLA‐DQB1 allele, HLA‐DQB1*0632
Authors: Emmerich F. , Schönemann C. , Diederich G. , Horn P. A. , Salama A.
Published: November 2007

A novel human leukocyte antigen‐DQ allele, DQB1*0632, was identified in a 68‐year‐old bone marrow transplantation candidate. DQB1*0632 differs from DQB1*0603 by one nucleotide change in exon 2 resulting in the amino acid exchange Gly → Arg.
Identification of a new HLA‐A*24 variant, A*2474, by sequence‐based typing in the Korean population
Authors: Kwon O. J. , Kim J. , Park K. , Oh J. W. , Park C.
Published: November 2007

A novel human leukocyte antigen, A*24 (HLA‐A*24), was identified in the Korean population. HLA‐A*2474 allele shows one nucleotide difference from A*24020101 in exon 2 at nucleotide position 186 (C → A), resulting in an amino acid change, Ser38Arg.
Placental p,p′‐dichlorodiphenyldichloroethylene and cord blood immune markers
Authors: Brooks Kevin , Hasan Hanem , Samineni Sridhar , Gangur Venu , Karmaus Wilfried
Published: November 2007

Placental p,p′‐dichlorodiphenyldichloroethylene (p,p′‐DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p′‐DDE was associated with a statistically significant increase in cord plasma interleukin (IL)‐13. Furthermore, both cord plasma IL‐4/interferon (IFN)‐γ and IL‐13/IFN‐γ ratios were significantly positively associated with placental p,p′‐DDE concentration.
Ass's milk in children with atopic dermatitis and cow's milk allergy: Crossover comparison with goat's milk
Authors: Vita Daniela , Passalacqua Giovanni , Di Pasquale Giuseppe , Caminiti Lucia , Crisafulli Giuseppe , Rulli Imma , Pajno Giovanni B.
Published: November 2007

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single‐blind, controlled, randomized crossover. Twenty‐eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS‐PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter‐group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM.
Mycobacterial infection and atopy in childhood: A systematic review
Authors: Obihara Charles C. , Bollen Casper W. , Beyers Nulda , Kimpen Jan L. L.
Published: November 2007

The epidemiological relation between mycobacterial infection and the prevalence of atopic disease in humans is still unclear. This is in contrast to studies in murine models in which a clear suppression of atopic symptoms was observed after exposure to mycobacteria or mycobacterial products. We therefore wanted to provide a systematic overview of the published literature on the relationship between mycobacterial infection and atopic disease and to evaluate the causal relationship in a meta‐analysis. The EMBASE and MEDLINE databases were searched systematically for papers published in the English literature (1966–2005) on the relation between mycobacterial infection and atopic disease. Original observational or interventional studies involving the paediatric population were included. Two authors independently reviewed articles for data on mycobacterial exposure and atopic disease outcome. Any differences were resolved by discussion. Of a total of 1201 hits, 23 studies (19 cross‐sectionals, three case–controls and one prospective cohort) met the inclusion criteria. Only a minority of studies (40%) observed an association between mycobacterial infection and the prevalence of atopic disease outcome. In the meta‐analysis, only studies containing data on mycobacterial exposure and atopic disease outcome variables were included. Only cross‐sectional studies, in which the relation between a positive tuberculin skin test and allergic symptoms was studied, observed statistically significant negative correlation (odds ratio 0.63; 95% confidence interval: 0.51–0.79). The results of this review show that the evidence of the relationship of mycobacterial infection and atopic disease is based on observations of cross‐sectional studies. In a meta‐analysis, calculations showed a high level of heterogeneity (I2) within studies with similar design making it difficult to pool effects. This may partly be explained by differences in the type and definition of mycobacterial infection and lack of uniformity in the definition of atopy. The results show that only a minority of studies in the literature shows any evidence of inverse relationship between mycobacterial exposure and atopic disease outcome. The fact that the present epidemiological evidence on the relationship between mycobacterial infection and the development of atopic disease is based mainly on cross‐sectional observational studies indicates the need for population‐based prospective studies to address this issue. This issue needs to be addressed in view of recent suggestions to developing mycobacterial‐based vaccines against atopic disease in the future.
Variation in pollen production and pollen viability in natural populations of gynodioecious Beta vulgaris ssp. maritima: evidence for a cost of restoration of male function?
Authors: DUFAŸ M. , VAUDEY V. , DE CAUWER I. , TOUZET P. , CUGUEN J. , ARNAUD J.‐F.
Published: November 2007

Gynodioecious species are defined by the co‐occurrence of two clearly separated categories of plants: females and hermaphrodites. The hermaphroditic category may, however, not be homogeneous, as male fitness may vary among hermaphrodites as a result of many biological factors. In this study, we analysed estimates of pollen quantity and viability in the gynodioecious Beta vulgaris ssp. maritima, comparing hermaphrodites bearing a male‐fertile cytotype and hermaphrodites bearing cytoplasmic male sterility (CMS) genes, which are counteracted by nuclear restoration factors. We show that: (i) pollen quantity continuously varies among restored hermaphrodites, suggesting a complex genetic determination of nuclear restoration; (ii) pollen viability was lower in restored (CMS) hermaphrodites than in non‐CMS hermaphrodites, probably because of incomplete restoration in some of these plants; and (iii) pollen quantity and viability also varied among hermaphrodites with male‐fertile cytotypes, possibly a result of a silent cost of restoration. Finally, we discuss the consequences of these results for pollen flow and the dynamics of gynodioecy.
The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease
Authors: SANJAY SRINIVAS , ANNIGERI RAJEEV A , SESHADRI RAJAGOPALAN , RAO BUDITHI SUBBA , PRAKASH KOWDLE C , MANI MUTHU KRISHNA
Published: November 2007

Aim: To compare natriuretic, kaliuretic, diuretic and free water clearance efficacy of continuousversusbolus intravenous furosemide administration in patients with chronic renal insufficiency.

Material and methods: In a prospective randomized cross‐over trial, 42 patients of chronic renal insufficiency were randomized to receive the same dose of intravenous furosemide as bolus and continuous infusion. The effects of bolus and intravenous administration of furosemide on the volume of urine, sodium and potassium excretion were assessed.

Results: Mean age was 53.6 ± 14 years and 23 (55%) were male. The mean modification of diet in renal disease glomerular filtration rate was 20.5 ± 17 mL/min per 1.73 m2. The urinary excretion of sodium in intravenous bolus and infusion was 98.1 ± 78 and 114.4 ± 100 mmol, respectively (P = 0.001). Total urinary volume following bolus and infusion of furosemide was 1064 ± 627 and 1170 ± 764 mL, respectively (0.001). The excretion of potassium was similar in bolus (15.8 ± 16.6) and infusion (14.3 ± 9) administration (P = 0.11). The fractional excretion of sodium was higher following infusion (16.63 ± 16.1) than bolus administration (12.87 ± 9) of furosemide (P = 0.016).

Conclusion: Continuous intravenous infusion of furosemide has significantly better natriuretic and diuretic effect than bolus administration of the same dose of the drug in patients with advanced chronic renal insufficiency.