bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential effects of a selective dopamine D1-like receptor agonist on motor activity and c-fos expression in the frontal-striatal circuitry of SHR and Wistar-Kyoto rats
Authors: Diaz Heijtz Rochellys , Castellanos F Xavier
Published: May 2006

Background

Molecular genetic studies suggest the dopamine D1 receptor (D1R) may be implicated in attention-deficit/hyperactivity disorder (ADHD). As little is known about the potential motor role of D1R in ADHD, animal models may provide important insights into this issue.

Methods

We investigated the effects of a full and selective D1R agonist, SKF-81297 (0.3, 3 and 10 mg/kg), on motor behaviour and expression of the plasticity-associated gene,c-fos, in habituated young adult male Spontaneously Hypertensive Rats (SHR), the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived).

Results

SHR rats were more behaviourally active than WKY rats after injection with vehicle. The 0.3 mg/kg dose of SKF-81297 increased motor behaviour (locomotion, sifting, rearing, and sniffing) in both SHR and WKY rats. Total grooming was also stimulated, but only in WKY rats. The same dose increasedc-fosmRNA expression in the piriform cortex of both strains. The 3 mg/kg dose increased sifting and sniffing in both strains. Locomotion was also stimulated towards the end of the testing period. The intermediate dose decreased total rearing in both strains, and produced a significant increase in c-fos mRNA in the striatum, nucleus accumbens, olfactory tuberculum, and in the cingulate, agranular insular and piriform cortices. The 10 mg/kg dose of SKF-81297 produced a biphasic effect on locomotion, which was characterized by an initial decrease followed by later stimulation. The latter stimulatory effect was more pronounced in SHR than in WKY rats when compared to their respective vehicle-injected groups. The 10 mg/kg dose also stimulated sifting and sniffing in both strains. Both the 3 and 10 mg/kg doses had no effect on total grooming. The 10 mg/kg dose induced significantly higher levels ofc-fosmRNA expression in the nucleus accumbens and adjacent cortical regions (but not striatum) of SHR when compared to WKY rats.

Conclusion

The present results suggest a potential alteration in D1R neurotransmission within the frontal-striatal circuitry of SHR involved in motor control. These findings extend our understanding of the molecular alterations in SHR, a heuristically useful model of ADHD.
Identifying Individuals at High Risk of Melanoma: A Practical Predictor of Absolute Risk
Authors: Fears Thomas R. , Guerry DuPont , Pfeiffer Ruth M. , Sagebiel Richard W. , Elder David E. , Halpern Allan , Holly Elizabeth A. , Hartge Patricia , Tucker Margaret A.
Published: May 2006

Purpose

We developed a model to estimate the 5-year absolute risk of melanoma to efficiently identify individuals at increased risk of melanoma for potential interventions.

Patients and Methods

We used data from a case-control study with 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia, PA and San Francisco, CA; matched controls were 945 patients from outpatient clinics with similar catchment areas. All participants underwent extensive interviews and skin examinations. We selected easily obtained clinical characteristics and responses to simple questions for study in order to develop sex-specific relative risk models. These models were combined with incidence and mortality rates by United States geographic areas to develop estimates of the absolute risk of developing melanoma within 5 years.

Results

Relative risk models yielded an attributable risk of 86% for men and 89% for women, using at most seven variables. Attributable risks did not vary by age, ultraviolet B flux or hours outdoors. The absolute individual risks varied widely, depending on age, other host characteristics, and geographic area. Individual absolute risk can be estimated using a program available online.

Conclusion

Our procedures allow for estimating the absolute risk of developing melanoma to assist in the identification of patients at high risk. Such high-risk individuals could undergo interventions including a complete skin examination, counseling to avoid sun exposures, regular self and professional surveillance, or participation in prevention trials. It is important to emphasize that these projections are not intended to identify current melanoma cases.
Characterization of the Nuclear Factor-κB Responsiveness of the Human dio2 Gene
Authors: Zeöld Anikó , Doleschall Márton , Haffner Michael C. , Capelo Luciane P. , Menyhért Judit , Liposits Zsolt , da Silva Wagner S. , Bianco Antonio C. , Kacskovics Imre , Fekete Csaba , Gereben Balázs
Published: May 2006

Type 2 iodothyronine deiodinase (D2) activates T4 by deiodination to T3, a process being the source of most T3 present in the brain. In the mediobasal hypothalamus, expression of the dio2 gene is potently activated by administration of bacterial lipopolysaccharide (LPS), which in turn mediates the modifications in thyroid homeostasis typically observed in patients with nonthyroidal illness syndrome. Here we show that LPS-induced D2 expression is also observed in human MSTO-211H cells that endogenously express D2. Exposure to LPS rapidly doubled D2 activity by a mechanism that was partially blocked by the nuclear factor-κB (NF-κB) inhibitor sulfasalazine. Next, the human dio2 5′-flanking region promoter assay was used in HC11 cells and the p65/NF-κB responsiveness mapped to the 3′ approximately 600-bp region of hdio2 5′-flanking region, with an approximately 15-fold induction. Semiquantitative EMSA identified the strongest NF-κB binding sites at the positions −683 bp (called no. 2) and −198 bp (no. 5) 5′ to the transcriptional starting site. Despite the very similar NF-κB binding affinity of these two sites, site-directed mutagenesis and promoter assay indicated that only site no. 5 possessed transactivation potency in the presence of the p65 subunit of NF-κB. Other cytokine mediators such as signal transducer and activator of transcription-3 (STAT3) or signal transducer and activator of transcription-5 (STAT5) did not induce transcription of the dio2 gene. Our results indicate that inflammatory signals regulate D2 expression predominantly via the NF-κB pathway in a direct transcriptional manner and could contribute to the changes in thyroid economy observed in nonthyroidal illness syndrome during infection.
Growth Hormone-Releasing Hormone (GHRH) Neurons in the Arcuate Nucleus (Arc) of the Hypothalamus Are Decreased in Transgenic Rats Whose Expression of Ghrelin Receptor Is Attenuated: Evidence that Ghrelin Receptor Is Involved in the Up-Regulation of GHRH Expression in the Arc
Authors: Mano-Otagiri Asuka , Nemoto Takahiro , Sekino Azusa , Yamauchi Naoko , Shuto Yujin , Sugihara Hitoshi , Oikawa Shinichi , Shibasaki Tamotsu
Published: May 2006

GH secretagogue (GHS)/ghrelin stimulates GH secretion by binding mainly to its receptor (GHS-R) on GHRH neurons in the arcuate nucleus (Arc) of the hypothalamus. GHRH, somatostatin, and neuropeptide Y (NPY) in the hypothalamus are involved in the regulatory mechanism of GH secretion. We previously created transgenic (Tg) rats whose GHS-R expression is reduced in the Arc, showing lower body weight and shorter nose-tail length. GH secretion is decreased in female Tg rats. To clarify how GHS-R affects GHRH expression in the Arc, we compared the numbers of GHS-R-positive, GHRH, and NPY neurons between Tg and wild-type rats. Immunohistochemical analysis showed that the numbers of GHS-R-positive neurons, GHRH neurons, and GHS-R-positive GHRH neurons were reduced in Tg rats, whereas the numbers of NPY neurons and GHS-R-positive NPY neurons did not differ between the two groups. The numbers of Fos-positive neurons and Fos-positive GHRH neurons in response to KP-102 were decreased in Tg rats. Competitive RT-PCR analysis of GHRH mRNA expression in the cultured hypothalamic neurons showed that KP-102 increased NPY mRNA expression level and that NPY decreased GHRH mRNA expression level. KP-102 increased GHRH mRNA expression level in the presence of anti-NPY IgG. GH increased somatostatin mRNA expression. Furthermore, GH and somatostatin decreased GHRH mRNA expression, whereas KP-102 showed no significant effect on somatostatin mRNA expression. These results suggest that GHS-R is involved in the up-regulation of GHRH and NPY expression and that NPY, somatostatin, and GH suppress GHRH expression. It is also suggested that the reduction of GHRH neurons of Tg rats is induced by a decrease in GHS-R expression.
Quantitative Structure-Activity Relationship of Various Endogenous Estrogen Metabolites for Human Estrogen Receptor α and β Subtypes: Insights into the Structural Determinants Favoring a Differential Subtype Binding
Authors: Zhu Bao Ting , Han Gui-Zhen , Shim Joong-Youn , Wen Yujing , Jiang Xiang-Rong
Published: May 2006

To search for endogenous estrogens that may have preferential binding affinity for human estrogen receptor (ER) α or β subtype and also to gain insights into the structural determinants favoring differential subtype binding, we studied the binding affinities of 74 natural or synthetic estrogens, including more than 50 steroidal analogs of estradiol-17β (E2) and estrone (E1) for human ERα and ERβ. Many of the endogenous estrogen metabolites retained varying degrees of similar binding affinity for ERα and ERβ, but some of them retained differential binding affinity for the two subtypes. For instance, several of the D-ring metabolites, such as 16α-hydroxyestradiol (estriol), 16β-hydroxyestradiol-17α, and 16-ketoestrone, had distinct preferential binding affinity for human ERβ over ERα (difference up to 18-fold). Notably, although E2 has nearly the highest and equal binding affinity for ERα and ERβ, E1 and 2-hydroxyestrone (two quantitatively predominant endogenous estrogens in nonpregnant woman) have preferential binding affinity for ERα over ERβ, whereas 16α-hydroxyestradiol (estriol) and other D-ring metabolites (quantitatively predominant endogenous estrogens formed during pregnancy) have preferential binding affinity for ERβ over ERα. Hence, facile metabolic conversion of parent hormone E2 to various metabolites under different physiological conditions may serve unique functions by providing differential activation of the ERα or ERβ signaling system. Lastly, our computational three-dimensional quantitative structure-activity relationship/comparative molecular field analysis of 47 steroidal estrogen analogs for human ERα and ERβ yielded useful information on the structural features that determine the preferential activation of the ERα and ERβ subtypes, which may aid in the rational design of selective ligands for each human ER subtype.
Influence of Dehydration on the Expression of Neuropeptide Y Y1 Receptors in Hypothalamic Magnocellular Neurons
Authors: Urban Janice H. , Leitermann Randy J. , DeJoseph M. Regina , Somponpun Suwit J. , Wolak Michael L. , Sladek Celia D.
Published: May 2006

Regulation of vasopressin (VP) and oxytocin (OT) secretion involves integration of neural signals from hypothalamic osmoreceptors, ascending catecholaminergic and peptidergic cell groups in the brain stem, and local and autoregulatory afferents. Neuropeptide Y (NPY) is one factor that stimulates the release of VP and OT from the supraoptic (SON) and paraventricular nuclei of the hypothalamus via activation of Y1 receptors (Y1R). The current studies were designed to assess the regulation and distribution of NPY Y1R expression in the SON of male rats that were either given 2% NaCl drinking water (24–72 h) or water deprived (48 h). Subjecting male rats to these conditions resulted in significant increases in both the number of cells expressing Y1R immunoreactivity (ir) and the amount of Y1R protein per cell within the SON. Y1R immunoreactivity was increased in the magnocellular but not medial parvocellular paraventricular nuclei, and Y1R mRNA levels were increased in the SON of salt-loaded rats. Subpopulations of both VP and OT cells in the hypothalamus express Y1R immunoreactivity and a greater percentage of VP-ir cells express Y1R after salt loading. To control for potential effects of dehydration-induced anorexia, a group of euhydrate animals was pair fed with animals consuming 2% NaCl. No detectable change in Y1R expression was observed in the SON of pair-fed animals, even though body weights were significantly lower than controls. These data demonstrate that NPY Y1R gene and protein expression are increased in the SON of salt-loaded and water-deprived animals and provide a mechanism whereby NPY can support VP/OT release during prolonged challenges to fluid homeostasis.
Sim1 Haploinsufficiency Impairs Melanocortin-Mediated Anorexia and Activation of Paraventricular Nucleus Neurons
Authors: Kublaoui Bassil M. , Holder J. Lloyd , Gemelli Terry , Zinn Andrew R.
Published: May 2006

Single-minded 1 (SIM1) is one of only six genes implicated in human monogenic obesity. Haploinsufficiency of this hypothalamic transcription factor is associated with hyperphagic obesity and increased linear growth in both humans and mice. Additionally, Sim1 heterozygous mice show enhanced hyperphagia and obesity in response to a high-fat diet. Thus the phenotype of Sim1 haploinsufficiency is similar to that of agouti yellow (Ay), and melanocortin 4 receptor (Mc4r) knockout mice, both of which are defective in hypothalamic melanocortin signaling. Sim1 and Mc4r are both expressed in the paraventricular nucleus (PVN). Here we report that Sim1 heterozygous mice, which have normal energy expenditure, are hyperphagic despite having elevated hypothalamic proopiomelanocortin (Pomc) expression. In response to the melanocortin agonist melanotan-2 (MTII) they exhibit a blunted suppression of feeding yet increase their energy expenditure normally. They also fail to activate PVN neurons in response to the drug at a dose that induces robust c-Fos expression in a subset of Sim1 PVN neurons in wild-type mice. The resistance to melanocortin signaling in Sim1 heterozygotes is not due to a reduced number of Sim1 neurons in the PVN. Hypothalamic Sim1 gene expression is induced by leptin and MTII treatment. Our results demonstrate that Sim1 heterozygotes are resistant to hypothalamic melanocortin signaling and suggest that Sim1-expressing PVN neurons regulate feeding, but not energy expenditure, in response to melanocortin signaling.
Haploinsufficiency at the Protein Kinase A RIα Gene Locus Leads to Fertility Defects in Male Mice and Men
Authors: Burton Kimberly A. , McDermott Deborah A. , Wilkes David , Poulsen Melissa N. , Nolan Michael A. , Goldstein Marc , Basson Craig T. , McKnight G. Stanley
Published: May 2006

Carney complex (CNC) is a familial multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxomas, and endocrine tumors. CNC is inherited as an autosomal dominant trait and is transmitted with greater frequency by women vs. men. Nearly two thirds of CNC patients are heterozygous for inactivating mutations in the gene encoding the protein kinase A (PKA) type Iα regulatory subunit (RIα), PRKAR1. We report here that male mice heterozygous for the Prkar1a gene have severely reduced fertility. Sperm from Prkar1a heterozygous mice are morphologically abnormal and reduced in number. Genetic rescue experiments reveal that this phenotype results from elevated PKA catalytic activity in germ cells as early as the pachytene stage of spermatogenesis. Consistent with this defect in the male mutant mice, sperm from CNC patients heterozygous for PRKAR1A mutations were also found to be morphologically aberrant and decreased in number. We conclude that unregulated PKA activity in male meiotic or postmeiotic germ cells leads to structural defects in mature sperm and results in reduced fertility in mice and humans, contributing to the strikingly reduced transmission of PRKAR1A inactivating mutations by male patients with CNC.
Nodal specifies embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning
Authors: Mesnard Daniel , Guzman-Ayala Marcela , Constam Daniel B.
Published: May 2006

Anteroposterior (AP) polarity in the mammalian embryo is specified during gastrulation when naive progenitor cells in the primitive ectoderm are recruited into the primitive streak to form mesoderm and endoderm. At the opposite pole, this process is inhibited by signals previously induced in distal visceral endoderm (DVE). Both DVE and primitive streak formation, and hence positioning of the AP axis, rely on the TGFβ family member Nodal and its proprotein convertases Furin and Pace4. Here, we show that Nodal and Furin are initially co-expressed in the primitive endoderm together with a subset of DVE markers such as Lefty1 and Hex. However, with the appearance of extra-embryonic ectoderm (ExE), DVE formation is transiently inhibited. During this stage, Nodal activity is essential to specify embryonic VE and restrict the expression of Furin to the extra-embryonic region. Activation of Nodal is also necessary to maintain determinants of pluripotency such as Oct4, Nanog and Foxd3 during implantation, and to stimulate elongation of the egg cylinder, before inducing DVE and germ layer formation. We conclude that Nodal is already activated in primitive endoderm, but induces a functional DVE only after promoting the expansion of embryonic VE and pluripotent progenitor cells in the epiblast.
Radial intercalation of ciliated cells duringXenopusskin development
Authors: Stubbs Jennifer L. , Davidson Lance , Keller Ray , Kintner Chris
Published: May 2006

Cells with motile cilia cover the skin of Xenopus tadpoles in a characteristic spacing pattern. This pattern arises during early development when cells within the inner layer of ectoderm are selected out by Notch to form ciliated cell precursors (CCPs) that then radially intercalate into the outer epithelial cell layer to form ciliated cells. When Notch is inhibited and CCPs are overproduced, radial intercalation becomes limiting and the spacing of ciliated cells is maintained. To determine why this is the case, we used confocal microscopy to image intercalating cells labeled using transplantation and a transgenic approach that labels CCPs with green fluorescent protein (GFP). Our results indicate that inner cells intercalate by first wedging between the basal surface of the outer epithelium but only insert apically at the vertices where multiple outer cells make contact. When overproduced, more CCPs are able to wedge basally, but apical insertion becomes limiting. We propose that limitations imposed by the outer layer,along with restrictions on the apical insertion of CCPs, determine their pattern of radial intercalation.
Phenotypic plasticity and evolution by genetic assimilation
Authors: Pigliucci Massimo , Murren Courtney J. , Schlichting Carl D.
Published: May 2006

In addition to considerable debate in the recent evolutionary literature about the limits of the Modern Synthesis of the 1930s and 1940s, there has also been theoretical and empirical interest in a variety of new and not so new concepts such as phenotypic plasticity, genetic assimilation and phenotypic accommodation. Here we consider examples of the arguments and counter-arguments that have shaped this discussion. We suggest that much of the controversy hinges on several misunderstandings, including unwarranted fears of a general attempt at overthrowing the Modern Synthesis paradigm, and some fundamental conceptual confusion about the proper roles of phenotypic plasticity and natural selection within evolutionary theory.
Functional, structural and molecular plasticity of mammalian skeletal muscle in response to exercise stimuli
Authors: Flück Martin
Published: May 2006

Biological systems have acquired effective adaptive strategies to cope with physiological challenges and to maximize biochemical processes under imposed constraints. Striated muscle tissue demonstrates a remarkable malleability and can adjust its metabolic and contractile makeup in response to alterations in functional demands. Activity-dependent muscle plasticity therefore represents a unique model to investigate the regulatory machinery underlying phenotypic adaptations in a fully differentiated tissue.

Adjustments in form and function of mammalian muscle have so far been characterized at a descriptive level, and several major themes have evolved. These imply that mechanical, metabolic and neuronal perturbations in recruited muscle groups relay to the specific processes being activated by the complex physiological stimulus of exercise. The important relationship between the phenotypic stimuli and consequent muscular modifications is reflected by coordinated differences at the transcript level that match structural and functional adjustments in the new training steady state. Permanent alterations of gene expression thus represent a major strategy for the integration of phenotypic stimuli into remodeling of muscle makeup.

A unifying theory on the molecular mechanism that connects the single exercise stimulus to the multi-faceted adjustments made after the repeated impact of the muscular stress remains elusive. Recently, master switches have been recognized that sense and transduce the individual physical and chemical perturbations induced by physiological challenges via signaling cascades to downstream gene expression events. Molecular observations on signaling systems also extend the long-known evidence for desensitization of the muscle response to endurance exercise after the repeated impact of the stimulus that occurs with training. Integrative approaches involving the manipulation of single factors and the systematic monitoring of downstream effects at multiple levels would appear to be the ultimate method for pinpointing the mechanism of muscle remodeling. The identification of the basic relationships underlying the malleability of muscle tissue is likely to be of relevance for our understanding of compensatory processes in other tissues, species and organisms.
Environment and plasticity of myogenesis in teleost fish
Authors: Johnston Ian A.
Published: May 2006

Embryonic development in teleosts is profoundly affected by environmental conditions, particularly temperature and dissolved oxygen concentrations. The environment determines the rate of myogenesis, the composition of sub-cellular organelles, patterns of gene expression, and the number and size distribution of muscle fibres. During the embryonic and larval stages, muscle plasticity to the environment is usually irreversible due to the rapid pace of ontogenetic change. In the early life stages, muscle can affect locomotory performance and behaviour, with potential consequences for larval survival. Postembryonic growth involves myogenic progenitor cells (MPCs) that originate in the embryo. The embryonic temperature regime can have long-term consequences for the growth of skeletal muscle in some species, including the duration and intensity of myotube formation in adult stages. In juvenile and adult fish,abiotic (temperature, day-length, water flow characteristics, hypoxia) and biotic factors (food availability, parasitic infection) have complex effects on the signalling pathways regulating the proliferation and differentiation of MPCs, protein synthesis and degradation, and patterns of gene expression. The phenotypic responses observed to the environment frequently vary during ontogeny and are integrated with endogenous physiological rhythms,particularly sexual maturation. Studies with model teleosts provide opportunities for investigating the underlying genetic mechanisms of muscle plasticity that can subsequently be applied to non-model species of more ecological or commercial interest.
Coordination of metabolic plasticity in skeletal muscle
Authors: Hood David A. , Irrcher Isabella , Ljubicic Vladimir , Joseph Anna-Maria
Published: May 2006

Skeletal muscle is a highly malleable tissue, capable of pronounced metabolic and morphological adaptations in response to contractile activity(i.e. exercise). Each bout of contractile activity results in a coordinated alteration in the expression of a variety of nuclear DNA and mitochondrial DNA(mtDNA) gene products, leading to phenotypic adaptations. This results in an increase in muscle mitochondrial volume and changes in organelle composition,referred to as mitochondrial biogenesis. The functional consequence of this biogenesis is an improved resistance to fatigue. Signals initiated by the exercise bout involve changes in intracellular Ca2+ as well as alterations in energy status (i.e. ATP/ADP ratio) and the consequent activation of downstream kinases such as AMP kinase and Ca2+-calmodulin-activated kinases. These kinases activate transcription factors that bind DNA to affect the transcription of genes, the most evident manifestation of which occurs during the post-exercise recovery period when energy metabolism is directed toward anabolism, rather than contractile activity. An important protein that is affected by exercise is the transcriptional coactivator PGC-1α, which cooperates with multiple transcription factors to induce the expression of nuclear genes encoding mitochondrial proteins. Once translated in the cytosol, these mitochondrially destined proteins are imported into the mitochondrial outer membrane, inner membrane or matrix space via specific import machinery transport components. Contractile activity affects the expression of the import machinery, as well as the kinetics of import, thus facilitating the entry of newly synthesized proteins into the expanding organelle. An important set of proteins that are imported are the mtDNA transcription factors, which influence the expression and replication of mtDNA. While mtDNA contributes only 13 proteins to the synthesis of the organelle, these proteins are vital for the proper assembly of multi-subunit complexes of the respiratory chain,when combined with nuclear-encoded protein subunits. The expansion of skeletal muscle mitochondria during organelle biogenesis involves the assembly of an interconnected network system (i.e. a mitochondrial reticulum). This expansion of membrane size is influenced by the balance between mitochondrial fusion and fission. Thus, mitochondrial biogenesis is an adaptive process that requires the coordination of multiple cellular events, including the transcription of two genomes, the synthesis of lipids and proteins and the stoichiometric assembly of multisubunit protein complexes into a functional respiratory chain. Impairments at any step can lead to defective electron transport, a subsequent failure of ATP production and an inability to maintain energy homeostasis.
Neuron–glia metabolic coupling and plasticity
Authors: Magistretti Pierre J.
Published: May 2006

The coupling between synaptic activity and glucose utilization(neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the `astrocyte–neuron lactate shuttle', is supported experimentally by a large body of evidence,which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron–glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity,involving by definition neuron–glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep–wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.
Phenotypic plasticity and experimental evolution
Authors: Garland Theodore , Kelly Scott A.
Published: May 2006

Natural or artificial selection that favors higher values of a particular trait within a given population should engender an evolutionary response that increases the mean value of the trait. For this prediction to hold, the phenotypic variance of the trait must be caused in part by additive effects of alleles segregating in the population, and also the trait must not be too strongly genetically correlated with other traits that are under selection. Another prediction, rarely discussed in the literature, is that directional selection should favor alleles that increase phenotypic plasticity in the direction of selection, where phenotypic plasticity is defined as the ability of one genotype to produce more than one phenotype when exposed to different environments. This prediction has received relatively little empirical attention. Nonetheless, many laboratory experiments impose selection regimes that could allow for the evolution of enhanced plasticity (e.g. desiccation trials with Drosophila that last for several hours or days). We review one example that involved culturing of Drosophila on lemon for multiple generations and then tested for enhanced plasticity of detoxifying enzymes. We also review an example with vertebrates that involves selective breeding for high voluntary activity levels in house mice, targeting wheel-running behavior on days 5+6 of a 6-day wheel exposure. This selection regime allows for the possibility of wheel running itself or subordinate traits that support such running to increase in plasticity over days 1–4 of wheel access. Indeed, some traits, such as the concentration of the glucose transporter GLUT4 in gastrocnemius muscle, do show enhanced plasticity in the selected lines over a 5–6 day period. In several experiments we have housed mice from both the Selected (S) and Control (C) lines with or without wheel access for several weeks to test for differences in plasticity (training effects). A variety of patterns were observed, including no training effects in either S or C mice, similar changes in both the S and C lines, greater changes in the S lines but in the same direction in the C lines, and even opposite directions of change in the S and C lines. For some of the traits that show a greater training effect in the S lines, but in the same direction as in C lines, the greater effect can be explained statistically by the greater wheel running exhibited by S lines (`more pain, more gain'). For others, however, the differences seem to reflect inherently greater plasticity in the S lines (i.e. for a given amount of stimulus, such as wheel running/day, individuals in the S lines show a greater response as compared with individuals in the C lines). We suggest that any selection experiment in which the selective event is more than instantaneous should explore whether plasticity in the appropriate (adaptive) direction has increased as a component of the response to selection.
Green chemistry: The development of cross-dehydrogenative coupling (CDC) for chemical synthesis
Authors: Li Chao-Jun , Li Zhiping
Published: May 2006

Social, economic, and environmental concerns about chemical production have been increasing. These concerns all originate from the inefficiency of conventional chemical syntheses. On the basis of the "E-factor", a concept of the "extended E-factor" is proposed in the article and is used to correlate various industrial sectors and the average number of synthetic steps involved in those sectors. Based on this analysis, the most fundamental way to eliminate waste formation is to develop new chemical reactivity that can greatly shorten the steps involved in a chemical synthesis. In classical organic transformations, a "functional group" is required. In efforts to develop new chemical reactivities that do not need extra steps for generating functional groups, we have recently developed various cross-dehydrogenative coupling (CDC) methodologies to construct functional molecules by directly using C-H bonds. This article describes the progress of our group's research endeavor.
Fate of anthropogenic organic pollutants in soils with emphasis on adsorption/desorption processes of endocrine disruptor compounds
Authors: Loffredo Elisabetta , Senesi Nicola
Published: May 2006

After providing a brief overview of the various phenomena that anthropogenic organic pollutants (AOPs) of various nature and origin are subjected to in soil, the paper focuses on an important class of these, the endocrine disruptor compounds (EDCs), which are hormone-like substances able to alter (i.e.) disrupt, the normal endocrine functions in animals and humans. EDCs may enter the soil through current agricultural practices andor disposal of urban and industrial effluents, sludges, and wastes. The estrogenic risk of EDCs is generally related to their distribution and speciation in the various soil phases, in which adsorption/desorption processes play a very important role. Adsorption kinetics and adsorption/desorption isotherms of the EDCs: bisphenol A (BPA), octylphenol (OP), 17-α-ethynilestradiol (EED), and 17-β-estradiol (17ED), onto four samples collected from the surface (depth 0-30 cm) and deep (depth 30-90 cm) horizons of two acidic sandy soils in Portugal (P) and Germany (G) (P30 and G30, and P90 and G90, respectively) were determined using a batch equilibrium method and the high-performance liquid chromatography (HPLC) technique. Adsorption of EDCs onto all soils examined occurs in two phases, a rapid one in less than 10 h of contact, and corresponding to more than 90 % of total adsorption, and a slow one that may need several hours until attainment of equilibrium. Experimental adsorption data fit best in a linear isotherm for BPA, in a nonlinear, L-shaped Freundlich isotherm for EED, in either a linear or a nonlinear Freundlich isotherm for OP, and in a Langmuir isotherm for 17ED. Thus, no limiting adsorption is observed for soils examined over the concentration range tested for BPA, OP, and EED, whereas a maximum adsorption (i.e., saturation) is reached only by 17ED. In general, the values of the Freundlich constant, K, and of the distribution coefficient, K
d, calculated from the experimental isotherms of the four EDCs onto soils examined follow the same trend, that is: G30 > P30 > P90 > G90. Further, the K and K
d values of any EDC are positively correlated with the soil organic carbon (OC) content, which is larger for surface horizon soils than deep horizon soils. Adsorption of BPA is generally reversible, and its desorption occurs quickly and completely, thus, it is expected to move down the soil profile, and possibly contaminate the groundwater. On the contrary, OP and EED are adsorbed almost irreversibly, and are slowly and only limitedly desorbed, thus are expected to accumulate, especially in the top soil layer, and cause soil contamination.
Asymmetric cyanohydrin synthesis from aldehydes and ketones using chiral metal (salen) complex as catalyst
Authors: Kim Sung Soo
Published: May 2006

Chiral Al(salen) is used as catalyst for enantioselective cyanosilylation of aldehydes and ketones.
Novel function of calreticulin: Characterization of calreticulin as a transacetylase-mediating protein acetylator independent of acetyl CoA using polyphenolic acetates
Authors: Raj Hanumantharao G. , Kumari Ranju , Seema  , Gupta Garima , Kumar Rajesh , Saluja Daman , Muralidhar Kambadoor M. , Kumar Ajit , Dwarkanath Bilikere S. , Rastogi Ramesh C. , Prasad Ashok K. , Patkar Shamkant A. , Watterson Arthur C. , Parmar Virinder S.
Published: May 2006

Our earlier investigations culminated in the discovery of a unique membrane-bound enzyme in mammalian cells catalyzing the transfer of acetyl group from polyphenolic acetates (PAs) to certain functional proteins, resulting in the modulation of their activities. This enzyme was termed acetoxy drug:protein transacetylase (TAase) since it acted upon several classes of PAs. TAase was purified from rat liver microsomes to homogeneity and exhibited the molecular weight of 55 KDa. TAase-catalyzed protein acetylation by PAs was evidenced by the demonstration of immunoreactivity of the acetylated target protein such as nitric oxide synthase (NOS) with anti-acetyl lysine. The possible acetylation of human platelet NOS by PA as described above resulted in the enhancement of intracellular levels of nitric oxide (NO). PAs unlike the parent polyphenols were found to exhibit NO-related physiological effects. The N-terminal sequence was found to show 100 % homology with N-terminal sequence of mature calreticulin (CRT). The identity of TAase with CRT, an endoplasmic reticulum (ER) protein, was evidenced by the demonstration of the properties of CRT such as immunoreactivity with anti-calreticulin, binding to Ca2+ ions and being substrate for phosphorylation by protein kinase c (PKC), which are the hallmark characteristics of CRT. These observations for the first time convincingly attribute the transacetylase function to CRT, which possibly plays an important role in protein modification by way of carrying out acetylation of various enzymes through a biochemical mechanism independent of acetyl CoA.
One-pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications
Authors: Xie Jin , Peng Sheng , Brower Nathan , Pourmand Nader , Wang Shan X. , Sun Shouheng
Published: May 2006

One-pot reaction of iron(III) acetylacetonate, Fe(acac)3, [or Fe(acac)3 and M(acac)2 where M = Mn and Co], with 1,2-alkanediol, oleic acid, and oleylamine in high boiling organic solvent leads to monodisperse ferrite MFe2O4 nanoparticles. Depending on the concentration of the metal precursors, surfactant-to-metal precursor ratio and the solvent used in the reaction, the particle size from this one-pot reaction can be tuned from 4 to 15 nm. The as-synthesized iron oxide nanoparticles have an inverse spinel structure, and their magnetic properties are controlled by particle size and M in the MFe2O4 structure. The hydrophobic iron oxide nanoparticles are readily transformed into hydrophilic ones by functional phospholipid addition to the as-synthesized particles and as a result, the monodisperse nanoparticles are readily functionalized with biotin, -COOH, -SH, and -NH2, facilitating their link to biomolecules for biomedical applications.
Physical techniques and catalyst preparation: Determining the interactions of transition-metal complexes with oxide surfaces
Authors: Carrier Xavier , Marceau Eric , Che Michel
Published: May 2006

This contribution presents the molecular approach used to investigate the different preparation steps of important catalytic systems, based on Mo, Ni, and Co. The first preparation step consists of impregnating oxide supports by aqueous solutions of transition-metal complexes (TMCs), called precursor complexes, and involves the liquid-solid (wet) interface. The following steps consist of thermal activation treatments, involving the gas-solid (dry) interface. The molecular approach is based on (i) the use of the TMC to monitor and probe the nature of its own interactions with the oxide support, (ii) the selection of the most appropriate techniques to monitor such interactions, and (iii) the design of experiments to identify and isolate the key parameters controlling the "TMC-oxide support" interactions.

Physical techniques play a key role in the characterization of catalyst preparation both at the macroscopic [temperature-programmed reduction (TPR), X-ray diffraction (XRD)] and molecular [Raman, X-ray absorption near-edge spectroscopy-extended X-ray absorption fine structure (XANES)-EXAFS, diffuse reflectance UV-vis] levels, particularly when they are used simultaneously. They give some insight into the structure of the species existing on the surface, with the oxide support behaving as a solid ligand, when exposed for a short time to the precursor complex solution or after thermal treatment, or, for longer contact times, as a reactant.
Novel instrumentation in electrochemical impedance spectroscopy and a full description of an electrochemical system
Authors: Park Su-Moon , Yoo Jung-Suk , Chang Byoung-Yong , Ahn Eun-Shil
Published: May 2006

The evolution of impedance measurement methods into the current state of the art is reviewed briefly, and recent efforts to develop new instruments to make electrochemical impedance spectroscopy (EIS) measurements faster and more accurate are described. The most recent approach for impedance measurement uses a multichannel detection technique, which is analogous to a spectroscopic measurement such as in Fourier transform infrared spectroscopy. This method, which is capable of making impedance measurements in real time during an electrochemical experiment, allows us to come up with a new integrated equation that makes a full description of an electrochemical system possible.
Prediction of leaching and groundwater contamination by pesticides
Authors: Kördel Werner , Klein Michael
Published: May 2006

Herein, we describe how pesticide leaching is assessed in Europe in order to fulfill EU Directive 91/414. The assessment schemes were developed to protect groundwater from unacceptable effects caused by pesticide use. They presently focus on chromatographic flow processes, which are dominant in sandy soils. Nevertheless, important regions in Europe are characterized by structured soils where transport through macropores is most relevant.

Comparison of parallel field studies with isoproturon performed in sandy and silty soils showed that maximum concentration in the structured soil at a soil depth of 1 m may exceed respective concentrations in sandy soils by a factor of 60. Similar results were obtained by lysimeter studies using silty soil cores with maximum concentration of 40 μg/l at the soil bottom. These results demonstrate that preferential flow is more the rule than the exception in well-structured fine-textured soils, and pesticide losses via macropore flow may exceed losses via matrix transport considerably. All present information available for macropore flow suggest the need for greater regional assessments. Other recommendations include analysis of the influence of different soil management practices on the formation of macropores.
Virus-Coated Layer-by-Layer Colloids as a Multiplex Suspension Array for the Detection and Quantification of Virus-Specific Antibodies
Authors: Toellner Lars , Fischlechner Martin , Ferko Boris , Grabherr Reingard Maria , Donath Edwin
Published: May 2006

Background: Suspension array technology has surpassed ELISA for automated, simultaneous detection and quantification of soluble biomarkers such as virus-specific antibodies. We describe assays in which antigens are attached to a lipid bilayer surrounding color-coded particles.

Methods: We used layer-by-layer technology to establish a multiplex suspension array with distinguishable microbeads coated with authentic viral surfaces to catch and quantify virus-specific antibodies in a flow cytometric analysis. Antigenic surfaces were generated by chimeric and wild-type baculoviruses plus 2 different influenza A virus subtypes fused to a lipid bilayer surrounding distinctly colored particles. Specificity of binding of chosen antibodies and sera was detected by immunofluorescence. Results of multiplex analysis were compared with results of ELISA.

Results: Titrations of virus-specific antibodies in the multiplex suspension array demonstrated specific binding to the viral surface proteins. The multiplex suspension array gave positive results for up to log 5–diluted primary antibodies with an ∼5- to 10-fold reduced dynamic range compared with the respective ELISA.

Conclusions: The bead-based multiplex suspension array is customizable and easy to establish. By displaying native influenza A virus surfaces and recombinant HIV-1 epitopes, the new assay provides a tool for the detection of major viral infections in humans.
Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Analysis of DNA on Microarrays
Authors: Kepper Pamela , Reinhardt Richard , Dahl Andreas , Lehrach Hans , Sauer Sascha
Published: May 2006

Background: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is a powerful tool in biomolecule analysis with a wide range of application possibilities, including genotyping of single-base variations (also known as single-nucleotide polymorphisms, or SNPs) for candidate gene studies and diagnostic typing of DNA markers. We tested a method that does not require stringent purification of the nucleic acids and/or the use of modification chemistry before mass spectrometry analysis.

Methods: We used an alternative direct analysis approach that allows MALDI analysis of crude DNA samples printed on microscope slides densely coated with primary amino groups that efficiently bind negatively charged DNA. After simple washing of the slides, we applied MALDI matrix and used a conventional MALDI mass spectrometer to detect DNA products.

Results: We analyzed crude oligonucleotide samples and performed automated genotyping of single-base variations in 72 DNA samples.

Conclusion: This procedure offers an operational short-cut compared with standard MALDI procedures for preparation of oligonucleotides, including purification, and thus is an efficient tool for genotyping applications, particularly those requiring accurate, flexible, and rapid data generation and medium throughput.
Evaluation of Disease Resistance of the Fish Lake–DeSmet, Wounded Man, and Harrison Lake Strains of Rainbow Trout Exposed to Myxobolus cerebralis
Authors: Wagner Eric J. , Wilson Chris , Arndt Ronney , Goddard Patrick , Miller Mark , Hodgson Ana , Vincent Richard , Mock Karen
Published: May 2006

Several tests evaluated the whirling disease resistance of three stocks of rainbow trout Oncorhynchus mykiss: the Fish Lake–DeSmet (FD), Wounded Man (WM), and Harrison Lake (HL) strains. In one series, FD fish were exposed to Myxobolus cerebralis triactinomyxons (TAMs; one exposure of 1,000 TAMs/fish). Histological scores ranged from 4.28 to 4.95 (MacConnnell−Baldwin scale) among FD fish from three different hatcheries. In addition, FD fish were exposed either acutely (1,000 TAMs/fish in one dose) or chronically (100 or 200 TAMs/fish on each of 10 d). There was no significant difference in mean myxospore counts among the three different exposure treatments. Histological scores ranged from 3.76 to 3.86 among the exposure groups and did not differ among exposure treatments. The correlation between histological scores and myxospore counts was significant (r = 0.57). Three different ages of WM rainbow trout were challenged with 1,000 TAMs/fish; histological scores for 62-d-old fish were significantly higher than scores for fish exposed at 108 or 137 d. Histological scores for WM fish did not significantly differ from those of HL fish, but both sets of scores were well below those of FD fish. The HL fry were exposed to doses of 0, 10, 100, 1,000, or 10,000 TAMs/fish. Histology scores were significantly different among treatments, ranging from 0.06 to 1.28 among the exposure groups. Even at doses of 1,000 or 10,000 TAMs/fish, a high percentage of fish had no or low pathology. Myxospore prevalence increased with dose: 7.5% at 10 TAMs/fish, 44.1% at 100 TAMs/fish, 70.0% at 1,000 TAMs/fish, and 87.7% at 10,000 TAMs/fish. Myxospore counts were significantly different among treatments, ranging from 0 to 540,556 among individual fish and from 514 to 75,380 among the treatment means of exposed groups. Deformities increased significantly with dose and ranged from 0.0% to 21.1%. Overall, FD rainbow trout showed little resistance to whirling disease, whereas the HL and WM strains included resistant individuals. Identification of resistant HL individuals for selective breeding could lead to a resistant broodstock.