bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin resistance shows selective metabolic and hormonal targets in the elderly
Authors: PAGANO G. , MARENA S. , SCAGLIONE L. , BODONI P. , MONTEGROSSO G. , BRUNO A. , CASSADER M. , BONETTI G. , PERIN P. CAVALLO
Published: March 2008

Abstract. There has been no simultaneous evaluation of different aspects of insulin action in ageing. We studied 12 elderly (77 ± 2 years) and 12 young (26 ±1 years) subjects with normal glucose tolerance and matched for sex, body mass index, lean body mass (LBM), blood pressure and physical activity, using a euglycaemic‐hyperinsulinaemic clamp at about 350 pmol L‐1 in combination with [3H]‐glucose infusion. In the elderly group, hepatic glucose production was normal, fasting serum insulin and C‐peptide were significantly increased (P= 0.001) and glucose utilization (34.4 ±2.4 vs. 44.4± 3.2 μmol kg‐1 LBM min‐1, P= 0.02) and the percentage maximal suppression of C‐peptide (58 ± 6% vs. 79 ±5%, P= 0.02) during the clamp were reduced. Fasting plasma free fatty acid (FFA) and glycerol levels were similar in the two groups, but their percentage maximal suppression during the clamp was reduced in the elderly group (FFA 45± 5% vs. 77 ± 6%, P= 0.001; glycerol 43 ± 5% vs. 76± 3%, P= 0.001). Branched‐chain amino acids (valine, leucine, isoleucine) and glucagon levels were similar in the two groups, both while fasting and during the clamp. Thus, insulin resistance in ageing appears selective on glucose utilization, inhibition of lipolysis and feedback inhibition of the B‐cell secretion.
Divergent effects of propranolol and nadolol in isolated mesenteric arteries from normal and portal hypertensive rats
Authors: STAUBER R. E. , HEINEMANN A. , TRAUNER M. , KREJS G. J.
Published: March 2008

Abstract. Propranolol, a non‐selective β‐blocker, is used for treatment of portal hypertension as it is believed to diminish splanchnic blood flow both by reducing cardiac output (β1‐blockade) and by increasing splanchnic arteriolar resistance (β2‐blockade). However, possible vasodilatory properties of propranolol at higher concentrations may counteract splanchnic vasoconstriction. Nadolol, another non‐selective β‐blocker, has also been suggested for treatment of portal hypertension. The aim of the present study was to investigate the effects of various concentrations of propranolol and nadolol on vascular resistance in isolated perfused mesenteric arterial beds from normal and portal hypertensive rats. At concentrations of 10‐7 mol L‐1 to 10‐6 mol L‐1 neither propranolol nor nadolol changed pressor responses to noradrenaline in normal rats. However, nadolol 10‐5 mol L‐1 significantly increased, whereas propranolol 10‐5 mol L‐1 reduced, noradrenaline‐induced vasoconstriction both in normal and in portal hypertensive rats. This unexpected vasodilatory effect of propranolol at high concentrations was present in preparations stimulated by both noradrenaline and methoxamine but not vasopressin and thus may be due to competitive α‐receptor blockade. In contrast, nadolol lacked this effect and produced splanchnic arteriolar vasoconstriction at high concentrations also.
New evidence that serum β2‐microglobulin behaves as a biological marker of bone remodelling in women
Authors: RIPOLL E. , REVILLA M. , HERNÁNDEZ E. R. , ARRIBAS I. , VILLA L. F. , RICO H.
Published: March 2008

Abstract. Having observed that serum β2‐microglobulin concentration correlates with serum tartrate‐resistant acid phosphatase (TRAP) concentration in postmenopausal osteoporosis, and that metacarpal endosteal diameter is dependent on bone resorption, we correlated the two biochemical parameters with the radiographic parameter to determine if β2‐microglobulin behaves like a biological marker of bone remodelling. In 105 women (mean age 68±4 years) consisting of 60 normal postmenopausal women and 55 osteoporotic postmenopausal women, there was a significant positive correlation between metacarpal endosteal diameter and these two biochemical values (r= 0.66 with β2‐microglobulin and r= 0.68 with TRAP in the osteoporotic postmenopausal women: r= 0.48 with β2‐microglobulin and r= 0.56 with TRAP in the normal postmenopausal women: P< 0.001 for all comparisons). All three measurements were significantly higher (P< 0.001) in the osteoporotic postmenopausal women than in the normal postmenopausal women. These findings show that serum β2‐microglobulin behaves like a biological marker of remodelling.
Longitudinal analysis of soluble intercellular adhesion molecule 1 in retinal vasculitis patients
Authors: PALMER H. E. , ZAMAN A. G. , ELLIS B. A. , STANFORD M. R. , GRAHAM E. M. , WALLACE G. R.
Published: March 2008

Abstract. Increased levels of soluble intercellular adhesion molecule 1 (sICAM‐1) in serum have been demonstrated in several human disease conditions. We have previously shown, in a point‐prevalence study, a positive correlation between sICAM‐1 levels and disease relapse in patients with idiopathic retinal vasculitis. We now report a longitudinal study over 1 year in which sICAM‐1 levels were compared with clinical disease status in order to determine this relationship further. Serum samples from 11 patients with idiopathic retinal vasculitis were tested for the presence of sICAM‐1 by enzyme linked immunosorbent assay. Eight control subjects were also tested. Five out of 11 patients presented with relapse and had raised sICAM‐1 levels compared with quiescent periods of their disease. Five out of 11 patients showed no relapse over 1 year and also no increase in sICAM‐1 levels. One patient showed increased levels of sICAM‐1, but no clinical signs of relapse. These results indicate that sICAM‐1 is associated with disease activity in retinal vasculitis patients and could indicate dysfunction of the blood‐retina barrier.
A meta‐analysis of latitudinal variations in life‐history traits of roach, Rutilus rutilus, over its geographical range: linear or non‐linear relationships?
Authors: LAPPALAINEN JYRKI , TARKAN ALI SERHAN , HARROD CHRIS
Published: March 2008

1. We collated information from the literature on life history traits of the roach (a generalist freshwater fish), and analysed variation in absolute fecundity, von Bertalanffy parameters, and reproductive lifespan in relation to latitude, using both linear and non‐linear regression models. We hypothesized that because most life history traits are dependent on growth rate, and growth rate is non‐linearly related with temperature, it was likely that when analysed over the whole distribution range of roach, variation in key life history traits would show non‐linear patterns with latitude.

2. As fecundity depends strongly on length, and the length structure of females varied among populations, latitudinal patterns in fecundity were examined based on residuals from the length–fecundity relationship. The reproductive lifespan of roach was estimated as the difference between age at maturity and maximum age of females in each population.

3. The three life history traits of roach analysed all varied among populations and were non‐linearly related to latitude. Only the relationship between reproductive lifespan and latitude was a better fit to a linear that to a quadratic model, although Loess smoothing curves revealed that this relationship was actually closer to biphasic than linear in form. A latitude of 50°N formed a break point in all three life history traits.

4. The negative relationships we have described between (i) fecundity and reproductive lifespan and (ii) fecundity and egg mass suggest that lower fecundity is compensated for by longer lifespan, while lower fecundity is compensated for by an increased egg mass, when analysed independently of location.
Future novel threats and opportunities facing UK biodiversity identified by horizon scanning
Authors: Sutherland William J. , Bailey Mark J. , Bainbridge Ian P. , Brereton Tom , Dick Jaimie T. A. , Drewitt Joanna , Dulvy Nicholas K. , Dusic Nicholas R. , Freckleton Robert P. , Gaston Kevin J. , Gilder Pam M. , Green Rhys E. , Heathwaite A. Louise , Johnson Sally M. , Macdonald David W. , Mitchell Roger , Osborn Daniel , Owen Roger P. , Pretty Jules , Prior Stephanie V. , Prosser Havard , Pullin Andrew S. , Rose Paul , Stott Andrew , Tew Tom , Thomas Chris D. , Thompson Des B. A. , Vickery Juliet A. , Walker Matt , Walmsley Clive , Warrington Stuart , Watkinson Andrew R. , Williams Rich J. , Woodroffe Rosie , Woodroof Harry J.
Published: March 2008

Horizon scanning is an essential tool for environmental scientists if they are to contribute to the evidence base for Government, its agencies and other decision makers to devise and implement environmental policies. The implication of not foreseeing issues that are foreseeable is illustrated by the contentious responses to genetically modified herbicide‐tolerant crops in the UK, and by challenges surrounding biofuels, foot and mouth disease, avian influenza and climate change.

A total of 35 representatives from organizations involved in environmental policy, academia, scientific journalism and horizon scanning were asked to use wide consultation to identify the future novel or step changes in threats to, and opportunities for, biodiversity that might arise in the UK up to 2050, but that had not been important in the recent past. At least 452 people were consulted.

Cases for 195 submitted issues were distributed to all participants for comments and additions. All issues were scored (probability, hazard, novelty and overall score) prior to a 2‐day workshop. Shortlisting to 41 issues and then the final 25 issues, together with refinement of these issues, took place at the workshop during another two rounds of discussion and scoring.

We provide summaries of the 25 shortlisted issues and outline the research needs.

We suggest that horizon scanning incorporating wide consultation with providers and users of environmental science is used by environmental policy makers and researchers. This can be used to identify gaps in knowledge and policy, and to identify future key issues for biodiversity, including those arising from outside the domains of ecology and biodiversity.

Synthesis and applications. Horizon scanning can be used by environmental policy makers and researchers to identify gaps in knowledge and policy. Drawing on the experience, expertise and research of policy advisors, academics and journalists, this exercise helps set the agenda for policy, practice and research.
Bacteriophage infection is targeted to cellular poles
Authors: Edgar Rotem , Rokney Assaf , Feeney Morgan , Semsey Szabolcs , Kessel Martin , Goldberg Marcia B. , Adhya Sankar , Oppenheim Amos B.
Published: March 2008

The poles of bacteria exhibit several specialized functions related to the mobilization of DNA and certain proteins. To monitor the infection of Escherichia coli cells by light microscopy, we developed procedures for the tagging of mature bacteriophages with quantum dots. Surprisingly, most of the infecting phages were found attached to the bacterial poles. This was true for a number of temperate and virulent phages of E. coli that use widely different receptors and for phages infecting Yersinia pseudotuberculosis and Vibrio cholerae. The infecting phages colocalized with the polar protein marker IcsA–GFP. ManY, an E. coli protein that is required for phage λ DNA injection, was found to localize to the bacterial poles as well. Furthermore, labelling of λ DNA during infection revealed that it is injected and replicated at the polar region of infection. The evolutionary benefits that lead to this remarkable preference for polar infections may be related to λ's developmental decision as well as to the function of poles in the ability of bacterial cells to communicate with their environment and in gene regulation.
Control of the cell elongation–division cycle by shuttling of PBP1 protein in Bacillus subtilis
Authors: Claessen Dennis , Emmins Robyn , Hamoen Leendert W. , Daniel Richard A. , Errington Jeff , Edwards David H.
Published: March 2008

The characteristic shape of bacterial cells is mainly determined by the cell wall, the synthesis of which is orchestrated by penicillin‐binding proteins (PBPs). Rod‐shaped bacteria have two distinct modes of cell wall synthesis, involved in cell elongation and cell division, which are believed to employ different sets of PBPs. A long‐held question has been how these different modes of growth are co‐ordinated in space and time. We have now identified the cell division protein, EzrA, and a newly discovered protein, GpsB, as key players in the elongation–division cycle of Bacillus subtilis. Mutations in these genes have a synthetic phenotype with defects in both cell division and cell elongation. They also have an unusual bulging phenotype apparently due to a failure in properly completing cell pole maturation. We show that these phenotypes are tightly associated with disturbed localization of the major transglycosylase/transpeptidase of the cell, PBP1. EzrA and GpsB have partially differentiated roles in the localization cycle of PBP1, with EzrA mainly promoting the recruitment of PBP1 to division sites, and GpsB facilitating its removal from the cell pole, after the completion of pole maturation.
The metabolic activity of Mycobacterium tuberculosis, assessed by use of a novel inducible GFP expression system, correlates with its capacity to inhibit phagosomal maturation and acidification in human macrophages
Authors: Lee Bai‐Yu , Clemens Daniel L. , Horwitz Marcus A.
Published: March 2008

Mycobacterium tuberculosis generally reside in phagosomes within human macrophages that resist maturation and acidification, but exhibit significant heterogeneity. In this study we have constructed an IPTG‐inducible GFP expression system in M. tuberculosis to assess the relationship between the metabolic status of M. tuberculosis and the degree of phagosomal maturation. Using these recombinant bacteria, we have found that, in human macrophages, M. tuberculosis that respond to IPTG with expression of GFP fluorescence, and hence are metabolically active, reside in non‐acidified phagosomes that have not fused with Texas red dextran pre‐labelled lysosomes. In contrast, M. tuberculosis that fail to express GFP in response to IPTG, and hence are metabolically inactive, reside within acidified phagosomes that have fused with Texas red dextran labelled lysosomes. These studies demonstrate that metabolic activity of M. tuberculosis correlates strongly with phagosomal maturation and that the inducible GFP expression system is useful for assessing metabolic activity of intracellular M. tuberculosis.
Altered plastid levels and potential for improved fruit nutrient content by downregulation of the tomato DDB1‐interacting protein CUL4
Authors: Wang Songhu , Liu Jikai , Feng Yuanyuan , Niu Xiangli , Giovannoni Jim , Liu Yongsheng
Published: March 2008

Fruits are a major source of nutrition in human diets, providing carbohydrates, fiber, vitamins and phytonutrients. Carotenoids are a principal class of compounds found in many fruits, providing nutritional benefits both as precursors to essential vitamins and as antioxidants. Molecular characterization revealed that the tomato high pigment mutant genes (hp1 and hp2) encode UV‐DAMAGED DNA BINDING PROTEIN‐1 (DDB1) and DE‐ETIOLATED‐1 (DET1) homologs, respectively, and both are essential components of the recently identified CUL4‐based E3 ligase complex. Here we have isolated a tomato CUL4 homolog and performed yeast two‐hybrid assays to suggest possible association of tomato DDB1 with CUL4 and DET1. Real‐time RT‐PCR analysis indicated that both HP1 and CUL4 are expressed constitutively. Abscisic acid is implicated in plastid division control and its application substantially enhances HP1/DDB1 mRNA accumulation. Transformation of constructs expressing CUL4–YFP and DDB1–YFP fusion proteins driven by the CaMV 35S promoter reveals that both CUL4 and DDB1 are targeted to tomato plastids and nuclei simultaneously. Using fruit‐specific promoters combined with RNAi technology, we show that downregulated DDB1 expression in transgenic fruits results in a significant increase in the number of plastids and corresponding enhanced pigment accumulation. CUL4‐RNAi repression lines provide insight regarding CUL4 function during tomato development, and reveal that this tomato cullin is important in the regulation of plastid number and pigmentation, which in turn have a direct impact on fruit nutrient quality.
DNA‐binding specificity, transcriptional activation potential, and the rin mutation effect for the tomato fruit‐ripening regulator RIN
Authors: Ito Yasuhiro , Kitagawa Mamiko , Ihashi Nao , Yabe Kimiko , Kimbara Junji , Yasuda Junichi , Ito Hirotaka , Inakuma Takahiro , Hiroi Seiji , Kasumi Takafumi
Published: March 2008

The RIN gene encodes a putative MADS box transcription factor that controls tomato fruit ripening, and its ripening inhibitor (rin) mutation yields non‐ripening fruit. In this study, the molecular properties of RIN and the rin mutant protein were clarified. The results revealed that the RIN protein accumulates in ripening fruit specifically and is localized in the nucleus of the cell. In vitro studies revealed that RIN forms a stable homodimer that binds to MADS domain‐specific DNA sites. Analysis of binding site selection experiments revealed that the consensus binding sites of RIN highly resemble those of the SEPALLATA (SEP) proteins, which are Arabidopsis MADS box proteins that control the identity of floral organs. RIN exhibited a transcription‐activating function similar to that exhibited by the SEP proteins. These results indicate that RIN exhibits similar molecular functions to SEP proteins although they play distinctly different biological roles. In vivo assays revealed that RIN binds to the cis‐element of LeACS2. Our results also revealed that the rin mutant protein accumulates in the mutant fruit and exhibits a DNA‐binding activity similar to that exhibited by the wild‐type protein, but has lost its transcription‐activating function, which in turn would inhibit ripening in mutant fruit.
A membrane‐bound NAC transcription factor NTL8 regulates gibberellic acid‐mediated salt signaling in Arabidopsis seed germination
Authors: Kim Sang‐Gyu , Lee An‐Kyo , Yoon Hye‐Kyung , Park Chung‐Mo
Published: March 2008

Gibberellic acid (GA) plays a key role in seed germination through coordinate interactions with other growth hormones and external signals. However, the way in which external signals are incorporated into the GA‐signaling pathway is largely unknown. Here, we demonstrate that a membrane‐bound NAC transcription factor NTL8 mediates the salt regulation of seed germination via the GA pathway, primarily independently of ABA. NTL8 is induced by high salinity. Its expression is also elevated by a GA biosynthetic inhibitor paclabutrazol (PAC), but is repressed by GA. Notably, high salinity greatly represses the GA3 oxidase 1 (GA3ox1) gene, supporting the hypothesis that salt signals inhibit seed germination by repressing GA biosynthesis. Induction of NTL8 and repression of GA3ox1 by high salinity still occur in the ABA‐deficient aba3‐1 mutant. Accordingly, the germination of a T‐DNA insertional ntl8‐1 mutant seed is resistant to high salinity and PAC. Interestingly, NTL8 is significantly induced during cold imbibition, but the induction declines quickly in germinating seeds, like RGL2. NTL8 activity is also regulated by controlled proteolytic release of the membrane‐bound NTL8 form. Its release from the membranes is activated by PAC and high salinity. Our data support that NTL8 modulates GA‐mediated salt signaling in regulating seed germination. This regulatory scheme may provide an adaptative fitness, which delays seed germination under high salinity conditions.
Ethylene regulates lateral root formation and auxin transport in Arabidopsis thaliana
Authors: Negi Sangeeta , Ivanchenko Maria G. , Muday Gloria K.
Published: March 2008

Lateral root branching is a genetically defined and environmentally regulated process. Auxin is required for lateral root formation, and mutants that are altered in auxin synthesis, transport or signaling often have lateral root defects. Crosstalk between auxin and ethylene in root elongation has been demonstrated, but interactions between these hormones in the regulation of Arabidopsis lateral root formation are not well characterized. This study utilized Arabidopsis mutants altered in ethylene signaling and synthesis to explore the role of ethylene in lateral root formation. We find that enhanced ethylene synthesis or signaling, through the eto1‐1 and ctr1‐1 mutations, or through the application of 1‐aminocyclopropane‐1‐carboxylic acid (ACC), negatively impacts lateral root formation, and is reversible by treatment with the ethylene antagonist, silver nitrate. In contrast, mutations that block ethylene responses, etr1‐3 and ein2‐5, enhance root formation and render it insensitive to the effect of ACC, even though these mutants have reduced root elongation at high ACC doses. ACC treatments or the eto1‐1 mutation significantly enhance radiolabeled indole‐3‐acetic acid (IAA) transport in both the acropetal and the basipetal directions. ein2‐5 and etr1‐3 have less acropetal IAA transport, and transport is no longer regulated by ACC. DR5‐GUS reporter expression is also altered by ACC treatment, which is consistent with transport differences. The aux1‐7 mutant, which has a defect in an IAA influx protein, is insensitive to the ethylene inhibition of root formation. aux1‐7 also has ACC‐insensitive acropetal and basipetal IAA transport, as well as altered DR5‐GUS expression, which is consistent with ethylene altering AUX1‐mediated IAA uptake, and thereby blocking lateral root formation.
Combined use of phenotypic and genotypic information in sampling animals for genotyping in detection of quantitative trait loci
Authors: Ansari‐Mahyari S. , Berg P.
Published: March 2008

Conventional selective genotyping which is using the extreme phenotypes (EP) was compared with alternative criteria to find the most informative animals for genotyping with respects to mapping quantitative trait loci (QTL). Alternative sampling strategies were based on minimizing the sampling error of the estimated QTL effect (MinERR) and maximizing likelihood ratio test (MaxLRT) using both phenotypic and genotypic information. In comparison, animals were randomly genotyped either within or across families. One hundred data sets were simulated each with 30 half‐sib families and 120 daughters per family. The strategies were compared in these datasets with respect to estimated effect and position of a QTL within a previously defined genomic region at genotyping 10, 20 or 30% of the animals. Combined linkage disequilibrium linkage analysis (LDLA) was applied in a variance component approach. Power to detect QTL was significantly higher for both MinERR and MaxLRT compared with EP and random genotyping methods (either across or within family), for all the proportions of genotyped animals. Power to detect significant QTL (α = 0.01) with 20% genotyping for MinERR and MaxLRT was 80 and 75% of that obtained with complete genotyping compared with 70 and 38% genotyping for EP within and across families respectively. With 30% genotyping, the powers were 78, 83, 78 and 58% respectively. The estimated variance components were unbiased in EP strategies (within and across family), only when at least 30% was genotyped. To decrease the number of genotyped individuals either MinERR or MaxLRT could be considered. With 20% genotyping in MinERR, the estimated QTL variance components were not significant compared with complete genotype information but all studied strategies at 20% genotyping overestimated the QTL effect. Results showed that combining the phenotypic and genotypic information in selective genotyping (e.g. MinERR and MaxLRT) is better than using only the EPs and the combined methods can be considered as alternative approaches to decrease genotyping costs, with unbiased QTL effects, decreased sampling variance of the QTL variance component and also increased the power of QTL detection.
Comparison of models for genetic evaluation of survival traits in dairy cattle: a simulation study
Authors: Jamrozik J. , Fatehi J. , Schaeffer L.R.
Published: March 2008

Three models for the analysis of functional survival data in dairy cattle were compared using stochastic simulation. The simulated phenotype for survival was defined as a month after the first calving (from 1 to 100) in which a cow was involuntarily removed from the herd. Parameters for simulation were based on survival data of the Canadian Jersey population. Three different levels of heritability of survival (0.100, 0.050 and 0.025) and two levels of numbers of females per generation (2000 or 4000) were considered in the simulation. Twenty generations of random mating and selection (on a second trait, uncorrelated with survival) with 20 replicates were simulated for each scenario. Sires were evaluated for survival of their daughters by three models: proportional hazard (PH), linear multiple‐trait (MT), and random regression (RR) animal models. Different models gave different ranking of sires with respect to survival of their daughters. Correlations between true and estimated breeding values for survival to five different points in a cow’s lifetime after the first calving (120 and 240 days in milk after first, second, third and fourth calving) favoured the PH model, followed by the RR model evaluations. Rankings of models were independent of the heritability level, female population size and sire progeny group size (20 or 100). The RR model, however, showed a slight superiority over MT and PH models in predicting the proportion of sire’s daughters that survived to the five different end‐points after the first calving.
Neural encoding of auditory temporal context in a songbird basal ganglia nucleus, and its independence of birds' song experience
Authors: Kojima Satoshi , Doupe Allison J.
Published: March 2008

Some of the most complex auditory neurons known are found in the songbird forebrain, throughout the ‘song system’, including its basal ganglia nucleus Area X. These cells are selective for the temporal order of the bird's own song (BOS): they typically respond strongly to BOS, but more weakly when the syllable sequence of BOS is played in reverse order (roBOS), indicating that they integrate auditory information over more than single syllables. Here, studying the zebra finch Area X, we found that order selectivity strongly depends on the mean syllable duration of individual songs, decreasing markedly as this duration approaches 150–200 ms. Simply segmenting the same songs differently, creating an increase in average syllable length towards 150 ms, caused a similar decrease in order selectivity. This suggests that song neurons integrate acoustic information over a relatively limited time window, predominantly less than 150 ms. We provided further support for this by showing that a significant fraction of Area X order selectivity was accounted for by the acoustic similarity between each BOS and roBOS, measured using cross‐correlation with fixed window sizes, but only when the correlation windows were at least 50 ms and no more than 200 ms long. All the same findings were evident in birds raised without tutor exposure, indicating that tutor learning has little effect on neural mechanisms underlying song temporal selectivity. Our results suggest that song‐selective neurons encode much of the temporal context of song using a short, constant time window that is conserved across differences in songs, birds and learning.
Postsynaptic µ‐opioid receptor response in the median preoptic nucleus is altered by a systemic sodium challenge in rats
Authors: Henry Mélaine , Drolet Guy , Mouginot Didier
Published: March 2008

The median preoptic nucleus (MnPO) is an integrator site for the chemosensory and neural signals induced by a perturbation in the hydromineral balance, and it is highly involved in controlling fluid and electrolyte ingestion. Here, we hypothesize that opioid peptides, previously recognized to control ingestive behaviors, may regulate the excitability of MnPO neurons and that this regulatory action may depend on the natriuric (Na+) status of body fluid compartments. Our results show that activation of µ‐, but not δ‐, opioid receptors (OR) triggered a membrane hyperpolarization by recruiting a G‐protein‐regulated inward‐rectifier K+ (GIRK) conductance in 41% of the neurons tested. Interestingly, 24 h Na+ depletion strengthened this opioid‐mediated control of neuronal excitability. In Na+‐depleted animals, the neuronal population displaying the µ‐OR‐induced hyperpolarization expanded to 60% (Z‐test, P = 0.012), whereas Na+ repletion restored this population to the control level (39%; Z‐test, P = 0.037). Among the neurons displaying µ‐OR‐induced hyperpolarization, Na+ depletion specifically increased the neuronal population responsive to variation in ambient Na+ (from 27% to 43%; Z‐test, P = 0.029). In contrast, Na+ repletion dramatically reduced the population that was unresponsive to Na+ (from 17% to 3%; Z‐test, P = 0.031). Neither the basic properties of the neurons nor the characteristics of the µ‐OR‐induced response were altered by the body Na+ challenge. Our results indicate that an episode of Na+ depletion/Na+ repletion modifies the organization of the opioid‐sensitive network of the MnPO. Such network plasticity might be related to the avid salt ingestion triggered by repeated Na+ depletion.
The spatio‐temporal and subcellular expression of the candidate Down syndrome gene Mnb/Dyrk1A in the developing mouse brain suggests distinct sequential roles in neuronal development
Authors: Hämmerle Barbara , Elizalde Carina , Tejedor Francisco J.
Published: March 2008

It is widely accepted that the neurological alterations in Down syndrome (DS) are principally due to modifications in developmental processes. Accordingly, a large part of the research on DS in recent years has focused on chromosome 21 genes that influence brain development. MNB/DYRK1A is one of the genes on human chromosome 21 that has raised most interest, due to its relationship with the brain functions that are altered in DS. Although a number of interesting experimental mouse models for DS are being developed, we still know little about the expression of Mnb/Dyrk1A during mouse brain development. Here, we report that Mnb/Dyrk1A displays a rather dynamic spatio‐temporal expression pattern during mouse central nervous system development. Our data indicate that Mnb/Dyrk1A is specifically expressed in four sequential developmental phases: transient expression in preneurogenic progenitors, cell cycle‐regulated expression in neurogenic progenitors, transient expression in recently born neurones, and persistent expression in late differentiating neurones. Our results also suggest that the subcellular localization of MNB/DYRK1A, including its translocation to the nucleus, is finely regulated. Thus, the MNB/DYRK1A protein kinase could be a key element in the molecular machinery that couples sequential events in neuronal development. This rich repertoire of potential functions in the developing central nervous system is suitable to be linked to the neurological alterations in DS through the use of mouse experimental models.
Matrix metalloproteinases MMP2 and MMP9 are upregulated by noradrenaline in the mouse neuroendocrine hypothalamus
Authors: Maolood N. , Hardin‐Pouzet H. , Grange‐Messent V.
Published: March 2008

Magnocellular neurons of the hypothalamic supraoptic nuclei (SON) are involved in the synthesis and release of two major neuropeptides: oxytocin (OT) and arginine‐vassopressin (AVP). Neurochemical plasticity in this system is induced by physiological conditions such as lactation, parturition and dehydration, and may be accompanied by reversible structural plasticity affecting neurons, astrocytes and the extracellular matrix (ECM). The noradrenergic system plays a critical role in triggering this chemical plasticity associated with structural plasticity. Matrix metalloproteinases (MMPs) are good candidates for involvement in the ECM remodelling observed in structural plasticity. We investigated the possible regulation of the two gelatinases, MMP2 and MMP9, by noradrenaline (NA) in the mouse neuroendocrine hypothalamus. We looked for the presence, location and activity of MMP2 and MMP9 in the SON, using anex vivoexperimental model of mouse hypothalamic slices incubated for 4 h with 10−4 mNA. We showed that: (i) immunoreactivity for MMP2 and MMP9 was detected not only in AVP‐positive and OT‐positive magnocellular neurons, but also in astrocyte processes in control and NA‐treated slices; (ii) the number of MMP2‐ and MMP9‐positive cells increased after incubation with NA; (iii) MMP2 and MMP9 displayed markedly higher levels of gelatinolytic activity after NA treatment. These results suggest that both MMP2 and MMP9 are regulated by NA, and could therefore also be involved in structural plasticity within the SON.
Volcanic calderas delineate biogeographic provinces among Yellowstone thermophiles
Authors: Takacs‐Vesbach Cristina , Mitchell Kendra , Jackson‐Weaver Olan , Reysenbach Anna‐Louise
Published: March 2008

It has been suggested that the distribution of microorganisms should be cosmopolitan because of their enormous capacity for dispersal. However, recent studies have revealed that geographically isolated microbial populations do exist. Geographic distance as a barrier to dispersal is most often invoked to explain these distributions. Here we show that unique and diverse sequences of the bacterial genus Sulfurihydrogenibium exist in Yellowstone thermal springs, indicating that these sites are geographically isolated. Although there was no correlation with geographic distance or the associated geochemistry of the springs, there was a strong historical signal. We found that the Yellowstone calderas, remnants of prehistoric volcanic eruptions, delineate biogeographical provinces for the Sulfurihydrogenibium within Yellowstone (χ2: 9.7, P = 0.002). The pattern of distribution that we have detected suggests that major geological events in the past 2 million years explain more of the variation in sequence diversity in this system than do contemporary factors such as habitat or geographic distance. These findings highlight the importance of historical legacies in determining contemporary microbial distributions and suggest that the same factors that determine the biogeography of macroorganisms are also evident among bacteria.
Maternal intimate partner violence and behavioural problems among Pacific children living in New Zealand
Authors: Paterson Janis , Carter Sarnia , Gao Wanzhen , Cowley‐Malcolm Esther , Iusitini Leon
Published: March 2008

Aims:  To examine (1) the association between maternal intimate partner violence (IPV) perpetration and victimisation and behavioural problems among two‐ and four‐year‐old Pacific children, and (2) the socio‐demographic and parenting factors that may impact on this association.

Design:  Mothers of the Pacific Islands Families (PIF) cohort of Pacific infants born in New Zealand during 2000 were interviewed when the children were two and four years of age. This data set was based on mothers who were cohabiting in married or de‐facto partnerships (N = 920) and who completed measures of IPV at the two‐year assessment point and the Child Behaviour Checklist (CBCL) at the two‐or four‐year assessment points. Of these, 709 mothers completed the CBCL at both assessment points.

Results:  There were no significant associations between IPV and the prevalence rates of clinically relevant cases of behavioural problems in the two‐year‐old child cohort. However, the prevalence rates of clinically relevant internalising, externalising and total problem cases were significantly higher among four‐year‐old children of mothers who reported severe perpetration of IPV. The odds of being in clinical range of internalising were 2.16 times higher for children of mothers who were perpetrators of severe physical violence than for those children of mothers who were not, and for externalising and total problems they were 2.38 and 2.36 times higher respectively. Socio‐demographic and parenting factors did not significantly influence the association between IPV and child behaviour problems.

Conclusion:  These findings contribute to the complex picture of the consequences that exposure to parental violence may have on the behaviour of young children. The effectiveness of preventative strategies may be maximised if implemented in these early years before such problems become entrenched and lead on to future behavioural problems and impaired family relationships.
‘Right from the Start’: randomized trial comparing an attachment group intervention to supportive home visiting
Authors: Niccols Alison
Published: March 2008

Background:  Infant attachment security is a protective factor for future mental health, and may be promoted by individual interventions. Given service demands, it is important to determine if a group‐based intervention for parents could be used to enhance infant attachment security.

Methods:  In a randomized trial involving 76 mothers, an 8‐session attachment group called ‘Right from the Start’ (RFTS) was compared to home visiting (treatment as usual).

Results:  Intention‐to‐treat analyses indicated no significant differences between RFTS and home visiting, with both groups showing small improvements in infant attachment security and maternal sensitivity. RFTS cost significantly less and was more cost effective than home visiting, and was not significantly different in terms of participation ratings, client satisfaction, or follow‐up service requests. There was differential compliance for the two interventions, with 89% and 58% attending 4 or more sessions of home visiting and RFTS, respectively. Secondary analyses considering non‐attenders as a separate (nonrandomized) group indicated a significant advantage for those who attended RFTS on pre‐test/post‐test maternal sensitivity change scores (d = .52) and pre‐test/6‐month follow‐up infant attachment security changes scores (d = .55).

Conclusions:  RFTS is as effective as home visiting in improving infant attachment security and maternal sensitivity. The effect sizes for RFTS were comparable to those of individual attachment interventions in this relatively inexpensive, community‐based group intervention.
Lysosomal release of cathepsins causes ischemic damage in the rat hippocampal slice and depends on NMDA‐mediated calcium influx, arachidonic acid metabolism, and free radical production
Authors: Windelborn James A. , Lipton Peter
Published: March 2008

NMDA‐mediated calcium entry and reactive oxygen species (ROS) production are well‐recognized perpetrators of ischemic neuronal damage. The current studies show that these events lead to the release of the protein hydrolase, cathepsin B, from lysosomes 2 h following 5‐min oxygen–glucose deprivation in the rat hippocampal slice. This release reflects a lysosomal membrane permeabilization (LMP) and was measured as the appearance of diffuse immunolabeled cathepsin B in the cytosol of CA1 pyramidal neurons. Necrotic neuronal damage begins after the release of cathepsins and is prevented by inhibitors of either cathepsin B or D indicating that the release of cathepsins is an important mediator of severe damage. There was an increase in superoxide levels, measured by dihydroethidium fluorescence, at the same time as LMP and reducing ROS levels with antioxidants, Trolox or N‐tert‐butyl‐α‐phenyl nitrone, blocked LMP. Both LMP and ROS production were blocked by an NMDA channel blocker (MK‐801) and by inhibitors of mitogen‐activated protein kinase kinase (U0126), calcium‐dependent/independent phospholipases A2 (methyl arachidonyl fluorophosphonate) but not calcium‐independent phospholipases A2 (bromoenol lactone) and cyclooxygenase‐2 (NS398). A cell‐permeant specific inhibitor of calpain (PD150606) prevented LMP, but not ROS production. It is concluded that LMP results in part from calcium‐initiated and extracellular signal‐regulated kinase‐initiated arachidonic acid metabolism, which produces free radicals; it also requires the action of calpain.
Regulation of Kv4.2 channels by glutamate in cultured hippocampal neurons
Authors: Lei Zhigang , Deng Ping , Xu Zao C.
Published: March 2008

Somatodendritic voltage‐dependent K+ currents (Kv4.2) channels mediate transient A‐type K+ currents and play critical roles in controlling neuronal excitability. Accumulating evidence has indicated that Kv4.2 channels are key regulatory components of the signaling pathways that lead to synaptic plasticity. In contrast to the extensive studies of glutamate‐induced AMPA [(±) α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid hydrate] receptors redistribution, less is known about the regulation of Kv4.2 by glutamate. In this study, we report that brief treatment with glutamate rapidly reduced total Kv4.2 levels in cultured hippocampal neurons. The glutamate effect was mimicked by NMDA, but not by AMPA. The effect of glutamate on Kv4.2 was dramatically attenuated by pre‐treatment of NMDA receptors antagonist MK‐801 [(5S,10R)‐(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine hydrogen maleate] or removal of extracellular Ca2+. Immunocytochemical analysis showed a loss of Kv4.2 clusters on the neuronal soma and dendrites following glutamate treatment, which was also dependent on the activation of NMDA receptors and the influx of Ca2+. Furthermore, whole‐cell patch‐clamp recordings revealed that glutamate caused a hyperpolarized shift in the inactivation curve of A‐type K+ currents, while the activation curve remained unchanged. These results demonstrate a glutamate‐induced alteration of Kv4.2 channels in cultured hippocampal neurons, which might be involved in activity‐dependent changes of neuronal excitability and synaptic plasticity.
Serotonin (5‐HT) induces glial cell line‐derived neurotrophic factor (GDNF) mRNA expression via the transactivation of fibroblast growth factor receptor 2 (FGFR2) in rat C6 glioma cells
Authors: Tsuchioka Mami , Takebayashi Minoru , Hisaoka Kazue , Maeda Natsuko , Nakata Yoshihiro
Published: March 2008

We previously reported that serotonin (5‐HT) increased glial cell line‐derived neurotrophic factor (GDNF) release in a 5‐HT2 receptor (5‐HT2R) and mitogen‐activated protein kinase kinase/extracellular signal‐related kinase (MEK/ERK)‐dependent manner in rat C6 glioma cells (C6 cells), a model of astrocytes. We herein found that 5‐HT‐induced rapid ERK phosphorylation was blocked by 5‐HT2R antagonists in C6 cells. We therefore examined 5‐HT‐induced ERK phosphorylation to reveal the mechanism of 5‐HT‐induced GDNF mRNA expression. As 5‐HT‐induced ERK phosphorylation was blocked by inhibitors for Gαq/11 and fibroblast growth factor receptor (FGFR), but not for second messengers downstream of Gαq/11, 5‐HT2R‐mediated FGFR transactivation was suggested to be involved in the ERK phosphorylation. Although FGFR1 and 2 were functionally expressed in C6 cells, 5‐HT selectively phosphorylated FGFR2. Indeed, small interfering RNA for FGFR2, but not for FGFR1, blocked 5‐HT‐induced ERK phosphorylation. As Src family tyrosine kinase inhibitors and microtubule depolymerizing agents blocked 5‐HT‐induced FGFR2 phosphorylation, Src family tyrosine kinase and stabilized microtubules were suggested to act upstream of FGFR2. Finally, 5‐HT‐induced GDNF mRNA expression was also inhibited by the blockade of 5‐HT2R, FGFR, and Src family tyrosine kinase. In conclusion, our findings suggest that 5‐HT induces GDNF mRNA expression via 5‐HT2R‐mediated FGFR2 transactivation in C6 cells.
Iron deficiency alters dopamine uptake and response to L‐DOPA injection in Sprague–Dawley rats
Authors: Bianco Laura E. , Wiesinger Jason , Earley Christopher J. , Jones Byron C. , Beard John L.
Published: March 2008

Iron deficiency (ID) disrupts brain dopamine (DA) and norepinephrine (NE) metabolism including functioning of monoamine transporters and receptors. We employed caudate microdialysis and no net flux (NNF) in post‐weaning rats to determine if ID decreased the extraction fraction (Ed). Five micromolar quinpirole, a dopamine D2 receptor agonist, resulted in 80% decrease in extracellular DA and 45% higher Ed in control animals. The D2 agonist had no effect on Ed in ID animals despite a reduction in basal DA. DAT mRNA levels were reduced by 58% with ID, while DAT protein in ventral midbrain and caudate and membrane associated DAT were also reduced by ID. Carbidopa/l‐DOPA was administered to determine if elevated extracellular DA in ID was due to increased release. The DA response to l‐DOPA in ID rats was 50% smaller and delayed, whereas the NE response was threefold higher. The caudate concentration of NE was also elevated in ID. Elevated dopamine‐β‐hydroxylase activity in ID provides a tentative explanation for the increased NE response to l‐DOPA. These experiments provide new evidence that ID results in altered synthesis and functioning of DAT and perhaps suggests some compensatory changes in NE metabolism.
Abnormal Polymorphonuclear Leukocyte Motility in Dermatologic Diseases
Authors: Harvath Liana
Published: March 2008

Abstract: A variety of skin diseases have been reported to have associated abnormalities in PMN chemotactic motility; however, the relationship of abnormal leukocyte motility to thc pathogenesis of these diseases is poorly understood. A common feature in skin diseases associated with depressed chemotaxis has been the frequency of recurrent pyogenic infections. Since the chemotaxins and methodologies for evaluating leukocyte chemotaxis differ among laboratories, little is knownabout the specificity of these chemotactic defects. Further information regarding PMN motility defects may be obtained from detailed studies of migration to various doses of chemotaxins. Thecommercial availability of potent, structurally defined chemotaxins, sueh a N‐formylatcd pcptides, provides laboratories the opportunity to evaluate migration to “common” chemotaxins. In addition, the development of the multiple microwell chemotaxis chamber has made possible the opportunity to collect substantial leukocyte motility data from relatively small blood samples. Further investigations of leukocyte motility in various dermatologic diseases are clearly needed, Amore systematic approaeh, i.e, (1) use of several different chemotaxins at various doses in chemotaxis assays and (2) use of standard, structurally defined chemotaxins. would facilitate com‐parative analyses of elinical studies among laboratories. It is likely that this approach would provide more specific information about the relevance of leukocyte motility defects in these diseases.
Anatomy and Embryology of the Eyelids: A Review with Special Reference to the Development of Divided Nevi
Authors: Hamming Nancy
Published: March 2008

In this review of the basie anatomy and embryology of thc human eyelids the sequence of eyelid differentiation is discussed. The development is important in exploring thc formation of divided or “kissing” nevi of the lids. Since the lids are fused from the ninth week until the twentieth week of gestation one may propose that the precursor elements of the nevus develop during that specific time. Because the epithelium only is fused, melanocytes derived from the neural crest must begin their differentiation in the region of the fused epithelium.