bluuebunny/crossref_metadata_2025 huggingface dataset:
Rectification and signal averaging of weak electric fields by biological cells.
Authors: Astumian R D , Weaver J C , Adair R K
Published: May 2006

Oscillating electric fields can be rectified by proteins in cell membranes to give rise to a dc transport of a substance across the membrane or a net conversion of a substrate to a product. This provides a basis for signal averaging and may be important for understanding the effects of weak extremely low frequency (ELF) electric fields on cellular systems. We consider the limits imposed by thermal and "excess" biological noise on the magnitude and exposure duration of such electric field-induced membrane activity. Under certain circumstances, the excess noise leads to an increase in the signal-to-noise ratio in a manner similar to processes labeled "stochastic resonance." Numerical results indicate that it is difficult to reconcile biological effects with low field strengths.
A progesterone metabolite stimulates the release of gonadotropin-releasing hormone from GT1-1 hypothalamic neurons via the gamma-aminobutyric acid type A receptor.
Authors: el-Etr M , Akwa Y , Fiddes R J , Robel P , Baulieu E E
Published: May 2006

The reduced progesterone metabolite tetrahydroprogesterone (3 alpha-hydroxy-5 alpha-pregnan-20-one; 3 alpha,5 alpha-THP) is a positive modulator of the gamma-aminobutyric acid type A (GABAA) receptor. Experiments performed in vitro with hypothalamic fragments have previously shown that GABA could modulate the release of gonadotropin-releasing hormone (GnRH). Using GT1-1 immortalized GnRH neurons, we investigated the role of GABAA receptor ligands, including 3 alpha,5 alpha-THP, on the release of GnRH. We first characterized the GABAA receptors expressed by these neurons. [3H]Muscimol, but not [3H]flunitrazepam, bound with high affinity to GT1-1 cell membranes (Kd = 10.9 +/- 0.3 nM; Bmax = 979 +/- 12 fmol/mg of protein), and [3H]muscimol binding was enhanced by 3 alpha,5 alpha-THP. mRNAs encoding the alpha 1 and beta 3 subunits of the GABAA receptor were detected by the reverse transcriptase polymerase chain reaction. In agreement with binding data, the benzodiazepine-binding gamma subunit mRNA was absent. GnRH release studies showed a dose-related stimulating action of muscimol. 3 alpha,5 alpha-THP not only modulated muscimol-induced secretion but also stimulated GnRH release when administered alone. Bicuculline and picrotoxin blocked the effects of 3 alpha,5 alpha-THP and muscimol. Finally, we observed that GT1-1 neurons convert progesterone to 3 alpha,5 alpha-THP. We propose that progesterone may increase the release of GnRH by a membrane mechanism, via its reduced metabolite 3 alpha,5 alpha-THP acting at the GABAA receptor.
Neurosteroids, via sigma receptors, modulate the [3H]norepinephrine release evoked by N-methyl-D-aspartate in the rat hippocampus.
Authors: Monnet F P , Mahé V , Robel P , Baulieu E E
Published: May 2006

N-Methyl-D-aspartate (NMDA, 200 microM) evokes the release of [3H]norepinephrine ([3H]NE) from preloaded hippocampal slices. This effect is potentiated by dehydroepiandrosterone sulfate (DHEA S), whereas it is inhibited by pregnenolone sulfate (PREG S) and the high-affinity sigma inverse agonist 1,3-di(2-tolyl)guanidine, at concentrations of > or = 100 nM. Neither 3 alpha-hydroxy-5 alpha-pregnan-20-one nor its sulfate ester modified NMDA-evoked [3H]NE overflow. The sigma antagonists haloperidol and 1-[2-(3,4-dichlorophenyl)-ethyl]-4-methylpiperazine, although inactive by themselves, completely prevented the effects of DHEA S, PREG S, and 1,3-di(2-tolyl)guanidine on NMDA-evoked [3H]NE release. Progesterone (100 nM) mimicked the antagonistic effect of haloperidol and 1-[2-(3,4-dichlorophenyl)ethyl]-4-methyl-piperazine. These results indicate that the tested steroid sulfate esters differentially affected the NMDA response in vitro and suggest that DHEA S acts as a sigma agonist, that PREG S acts as a sigma inverse agonist, and that progesterone may act as a sigma antagonist. Pertussis toxin, which inactivates the Gi/o types of guanine nucleotide-binding protein (Gi/o protein) function, suppresses both effects of DHEA S and PREG S. Since sigma 1 but not sigma 2 receptors are coupled to Gi/o proteins, the present results suggest that DHEA S and PREG S control the NMDA response via sigma 1 receptors.
A gene encoding a phosphatidylinositol-specific phospholipase C is induced by dehydration and salt stress in Arabidopsis thaliana.
Authors: Hirayama T , Ohto C , Mizoguchi T , Shinozaki K
Published: May 2006

A cDNA corresponding to a putative phosphatidylinositol-specific phospholipase C (PI-PLC) in the higher plant Arabidopsis thaliana was cloned by use of the polymerase chain reaction. The cDNA, designated cAtPLC1, encodes a putative polypeptide of 561 aa with a calculated molecular mass of 64 kDa. The putative product includes so-called X and Y domains found in all PI-PLCs identified to date. In mammalian cells, there are three types of PI-PLC, PLC-beta, -gamma, and -delta. The overall structure of the putative AtPLC1 protein is most similar to that of PLC-delta, although the AtPLC1 protein is much smaller than PLCs from other organisms. The recombinant AtPLC1 protein synthesized in Escherichia coli was able to hydrolyze phosphatidylinositol 4,5-bisphosphate and this activity was completely dependent on Ca2+, as observed also for mammalian PI-PLCs. These results suggest that the AtPLC1 gene encodes a genuine PI-PLC of a higher plant. Northern blot analysis showed that the AtPLC1 gene is expressed at very low levels in the plant under normal conditions but is induced to a significant extent under various environmental stresses, such as dehydration, salinity, and low temperature. These observations suggest that AtPLC1 might be involved in the signal-transduction pathways of environmental stresses and that an increase in the level of AtPLC1 might amplify the signal, in a manner that contributes to the adaptation of the plant to these stresses.
A simple p53 functional assay for screening cell lines, blood, and tumors.
Authors: Flaman J M , Frebourg T , Moreau V , Charbonnier F , Martin C , Chappuis P , Sappino A P , Limacher I M , Bron L , Benhattar J
Published: May 2006

Mutations in the p53 gene are implicated in the pathogenesis of half of all human tumors. We have developed a simple functional assay for p53 mutation in which human p53 expressed in Saccharomyces cerevisiae activates transcription of the ADE2 gene. Consequently, yeast colonies containing wild-type p53 are white and colonies containing mutant p53 are red. Since this assay tests the critical biological function of p53, it can distinguish inactivating mutations from functionally silent mutations. By combining this approach with gap repair techniques in which unpurified p53 reverse transcription-PCR products are cloned by homologous recombination in vivo it is possible to screen large numbers of samples and multiple clones per sample for biologically important mutations. This means that mutations can be detected in tumor specimens contaminated with large amounts of normal tissue. In addition, the assay detects temperature-sensitive mutants, which give pink colonies. We show here that this form of p53 functional assay can be used rapidly to detect germline mutations in blood samples, somatic mutations in tumors, and mutations in cell lines.
TPX2 is required for postmitotic nuclear assembly in cell-free Xenopus laevis egg extracts
Authors: O'Brien Lori L. , Wiese Christiane
Published: May 2006

Cell division in many metazoa is accompanied by the disassembly of the nuclear envelope and the assembly of the mitotic spindle. These dramatic structural rearrangements are reversed after mitosis, when the mitotic spindle is dismantled and the nuclear envelope reassembles. The targeting protein for XKlp2 (TPX2) plays important roles in mitotic spindle assembly. We report that TPX2 depletion from nuclear assembly extracts prepared from Xenopus laevis eggs results in the formation of nuclei that are only about one fifth the size of control nuclei. TPX2-depleted nuclei assemble nuclear envelopes, nuclear pore complexes, and a lamina, and they perform nuclear-specific functions, including DNA replication. We show that TPX2 interacts with lamina-associated polypeptide 2 (LAP2), a protein known to be required for nuclear assembly in interphase extracts and in vitro. LAP2 localization is disrupted in TPX2-depleted nuclei, suggesting that the interaction between TPX2 and LAP2 is required for postmitotic nuclear reformation.
Plasmacytoid dendritic cell–specific receptor ILT7–FcεRIγ inhibits Toll-like receptor–induced interferon production
Authors: Cao Wei , Rosen David B. , Ito Tomoki , Bover Laura , Bao Musheng , Watanabe Gokuran , Yao Zhengbin , Zhang Li , Lanier Lewis L. , Liu Yong-Jun
Published: May 2006

Immunoglobulin-like transcripts are a family of inhibitory and stimulatory cell surface immune receptors. Transcripts for one member of this family, ILT7, are selectively expressed in human plasmacytoid dendritic cells (pDCs). We demonstrate here that ILT7 protein associates with the signal adapter protein FcεRIγ to form a receptor complex. Using an anti-ILT7 monoclonal antibody, we show that ILT7 is expressed specifically on human pDCs, but not on myeloid dendritic cells or other peripheral blood leukocytes. Cross-linking of ILT7 resulted in phosphorylation of Src family kinases and Syk kinase and induced a calcium influx in freshly isolated pDCs, which was blocked by Src family and Syk kinases inhibitors, thus indicating the activation of an immunoreceptor-based tyrosine activation motif–mediated signaling pathway. ILT7 cross-linking on CpG or influenza virus-stimulated primary pDCs inhibited the transcription and secretion of type I interferon and other cytokines. Therefore, the ILT7–FcεRIγ receptor complex negatively regulates the innate immune functions of human pDCs.
Diversity within the current algal species Prototheca zopfii: a proposal for two Prototheca zopfii genotypes and description of a novel species, Prototheca blaschkeae sp. nov.
Authors: Roesler Uwe , Möller Asia , Hensel Andreas , Baumann Daniela , Truyen Uwe
Published: May 2006

In order to clarify the intraspecies taxonomic position of the non-photosynthetic algal species Prototheca zopfii, as well as the aetiology of bovine mammary protothecosis, a selection of P. zopfii strains isolated from clinical cases of protothecal mastitis and from various environmental habitats was characterized using a polyphasic molecular approach. Based on sequence analysis of the 18S rRNA gene, which showed distinct differences between the three currently known biotypes or ‘variants’, specific oligonucleotides were designed and used in biotype-specific PCRs. Furthermore, the pattern of cellular fatty acids was evaluated. Typing by means of these techniques revealed that the previously defined biotypes of P. zopfii were clearly different. Based on sequence analysis, the pattern of fatty acids and physiological characteristics, it is proposed that biotype 3 should be reclassified as representing a novel species, Prototheca blaschkeae sp. nov. (type strain, RZIII-3T=SAG 2064T). Furthermore, it is proposed that P. zopfii merits reclassification as a species comprising at least two genotypes that in future could probably be considered to represent two subspecies.
Herbaspirillum hiltneri sp. nov., isolated from surface-sterilized wheat roots
Authors: Rothballer Michael , Schmid Michael , Klein Ilona , Gattinger Andreas , Grundmann Sabine , Hartmann Anton
Published: May 2006

The genus Herbaspirillum of the Betaproteobacteria mainly comprises diazotrophic bacteria with a potential for endophytic and systemic colonization of a variety of plants. The plant-associated bacterial isolates N3T, N5 and N9 were derived from surface-sterilized wheat roots. After phylogenetic analysis of 16S rRNA gene sequence data the isolates could be allocated to the genus Herbaspirillum, and 99.9 % similarity to the sequence of Herbaspirillum lusitanum P6-12T was found. A set of 16S rRNA gene-targeted oligonucleotide probes was developed for the identification of the three novel isolates and H. lusitanum (Hhilu446), and for the specific detection of several other Herbaspirillum species described recently. For higher phylogenetic resolution, the 23S rRNA gene sequences of all members of the genus was sequenced and used to construct a phylogenetic tree. Isolates N3T, N5 and N9 formed a group that was distinct from all other Herbaspirillum species. In addition, isolate N3T and H. lusitanum P6-12T exhibited a DNA–DNA hybridization value of only 25 %. The value for DNA–DNA hybridization between N3T and other members of the genus Herbaspirillum was between 14 and 32 %; DNA–DNA hybridization between strain N3T and isolates N5 and N9 produced values above 95 %. This places the three isolates as representatives of a novel species within the genus Herbaspirillum. A Biolog GN2 assay supported this conclusion. The major fatty acids were C16 : 1
ω7c, C16 : 0 and C18 : 1
ω7c, and the DNA G+C content ranged from 60.9 to 61.5 mol%. Therefore these three isolates should be classified within a novel species, for which the name Herbaspirillum hiltneri sp. nov. is proposed. The type strain is N3T (=DSM 17495T=LMG 23131T).
Ornithinibacillus gen. nov., with the species Ornithinibacillus bavariensis sp. nov. and Ornithinibacillus californiensis sp. nov.
Authors: Mayr R. , Busse H.-J. , Worliczek H. L. , Ehling-Schulz M. , Scherer S.
Published: May 2006

A Gram-positive, aerobic, rod-shaped, motile, endospore-forming bacterium was isolated from pasteurized milk from Bavaria, Germany. 16S rRNA gene sequence similarities indicated that strain WSBC 24001T was most closely related to Virgibacillus species (95.3–96.1 %), Oceanobacillus species (95.6–95.7 %), Bacillus firmus IAM 12464T (95.5 %) and Bacillus niacini IFO 15566T (95.2 %). However, strain WSBC 24001T showed the highest level of sequence similarity to an unnamed strain, MB-9T (97.6 %), which was isolated from coastal surface sediments in California. Hence, this strain was included in our study. The genomic DNA G+C contents of strains WSBC 24001T and MB-9T were 36.4 mol and 40.8 mol%, respectively. The major respiratory quinone of both strains was menaquinone MK-7 and the peptidoglycan type was A4β (l-orn←d-Asp). The polar lipid profiles of these strains contained a predominance of diphosphatidylglycerol and moderate to minor amounts of phosphatidylglycerol, an unknown phospholipid and an unknown aminophospholipid. However, strain WSBC 24001T could be distinguished from strain MB-9T by the presence of an unknown lipid. The fatty acid profiles of the two strains comprised mainly iso- and anteiso-branched acids, but showed some significant quantitative differences in the amounts of certain acids. The DNA–DNA relatedness value (15.5 %) clearly demonstrated that strains WSBC 24001T and MB-9T are representatives of two different species. On the basis of their phylogenetic position and morphological, physiological and chemotaxonomic properties, a novel genus is proposed, Ornithinibacillus gen. nov., with two novel species, the type species Ornithinibacillus bavariensis sp. nov. (type strain WSBC 24001T=DSM 15681T=CCM 7096T) and Ornithinibacillus californiensis sp. nov. (type strain MB-9T=DSM 16628T=CCM 7237T).
Caldalkalibacillus thermarum gen. nov., sp. nov., a novel alkalithermophilic bacterium from a hot spring in China
Authors: Xue Yanfen , Zhang Xinqi , Zhou Cheng , Zhao Yueju , Cowan Don A. , Heaphy Shaun , Grant William D. , Jones Brian E. , Ventosa Antonio , Ma Yanhe
Published: May 2006

A thermophilic, alkaliphilic and catalase-positive bacterium, designated strain HA6T, was isolated from a hot spring in China. The strain was aerobic and chemo-organotrophic and grew optimally at 60 °C, pH 8.5 and 1.5 % (w/v) NaCl. The cells were Gram-positive rods, forming single terminal endospores. The predominant cellular fatty acids were iso-C15 : 0and iso-C17 : 0. The cell-wall peptidoglycan containedmeso-diaminopimelic acid. The genomic DNA G+C content was 45.2 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain HA6Tformed a distinct lineage within the familyBacillaceaeand was most closely related toBacillus hortiK13TandBacillus smithiiDSM 4216T, with sequence similarities of 91.8 and 93.1 %, respectively. On the basis of its physiological and molecular properties, strain HA6Tshould be placed in a novel genus and species, for which the nameCaldalkalibacillus thermarumgen. nov., sp. nov. is proposed. The type strain ofCaldalkalibacillus thermarumis strain HA6T(=CGMCC 1.4242T=JCM 13486T).
Anopheles gambiae P450 reductase is highly expressed in oenocytes and in vivo knockdown increases permethrin susceptibility
Authors: Lycett G. J. , McLaughlin L. A. , Ranson H. , Hemingway J. , Kafatos F. C. , Loukeris T. G. , Paine M. J. I.
Published: May 2006

We describe an in vivo model for investigation of detoxification mechanisms of the mosquito Anopheles gambiae, important for the development of malaria control programmes. Cytochrome P450s are involved in metabolic insecticide resistance and require NADPH cytochrome P450 reductase (CPR) to function. Here we demonstrate that the major sites of adult mosquito CPR expression are oenocytes, mid‐gut epithelia and head appendages. High CPR expression was also evident in Drosophila oenocytes indicating a general functional role in these insect cells. RNAi mediated knockdown drastically reduced CPR expression in oenocytes, and to a lesser extent in mid‐gut epithelia; the head was unaffected. These flies showed enhanced sensitivity to permethrin, demonstrating a key role for abdominal/mid‐gut P450s in pyrethroid metabolism, aiding the development of insecticides.
The determination of phenylalanine content of foods suitable for phenylketonuria
Authors: Weetch E. , MacDonald A.
Published: May 2006

Background  A low phenylalanine diet for people with phenylketonuria (PKU) is very restrictive. Natural foods allowed are based chiefly on fruits and vegetables but there is limited analysis on the phenylalanine content of newer and exotic fruit and vegetables. The assumption that 1 g protein yields 50 mg phenylalanine does not apply to fruits and vegetables.

Methods  The National Society for Phenylketonuria Medical Advisory Panel commissioned the phenylalanine analysis of 172 foods, which emphasis on fruit and vegetables. The foods were purchased from retail outlets and analysed by LGC Limited (67 foods) and the LFI (105 foods).

Results  There was a strong correlation between this phenylalanine and UK analyses published in 1980, but previous analysis included only a limited range of fruits and vegetables (r = 0.8746; P < 0.0001). There was also correlation between phenylalanine and UK protein analyses (r = 0.7976; P < 0.0001).

Conclusion  This new phenylalanine data have enabled a wider range of fruits and vegetables to be safely incorporated into the diet of people with PKU.
Somatic Hypermutation of Ig Genes is Affected Differently by Failures in Apoptosis Caused by Disruption of Fas (lpr Mutation) or by Overexpression of Bcl‐2
Authors: Mastache E. F. , Lindroth K. , Fernández C. , González‐Fernández Á.
Published: May 2006

The effects of the two main apoptotic pathways on the somatic hypermutation process were analysed. Transgenic mice carrying the VκOx1‐Jκ5 rat transgene were crossed with Fas‐deficient lpr mice or with mice overexpressing the Bcl‐2 protein. The transgenic VκOx1 segment and the endogenous JH4‐Cµ Ig intron from Peyer's patches germinal centre B cells were sequenced to study the intrinsic somatic hypermutation process without the skewing effects of specific antigen selection. The lpr/ox mice displayed, in both regions, a high level of mutations with a normal pattern of substitutions. On the contrary, the bcl‐2/ox mice displayed a lower level of mutations with an altered pattern, showing a decreased mutational rate in the intrinsic hotspots of the VκOx1 gene. Our results suggest that the lpr mutation does not have a direct effect on the somatic hypermutation process, but rather on the negative selection of B cells in the germinal centres, leading to the accumulation of recurrent mutations. In contrast, Bcl‐2 overexpression might influence the somatic hypermutational process either by altering the incorporation of mutations or by enhancing the repair mechanism(s). The present work supports the hypothesis that both apoptotic pathways, Fas and Bcl‐2, play distinct roles in the germinal centre reactions.
Blood groups and transfusions in pigs
Authors: Smith Douglas M. , Newhouse Michael , Naziruddin Bashoo , Kresie Lesley
Published: May 2006

Smith DM, Newhouse M, Naziruddin B, Kresie L. Blood groups and transfusions in pigs. Xenotransplantation 2006; 13: 186–194. © Blackwell Munksgaard, 2006

Abstract:  The blood groups of pigs are important to transplantation research because some are also important transplantation antigens and because pigs undergoing organ or hematopoietic transplantation may require transfusion support. There is considerable literature on the subject but much of it is not in transplant related journals. We will review this literature and also give some practical advice on transfusion support.
Current status of oxygen carriers (‘blood substitutes’): 2006
Authors: Winslow R. M.
Published: May 2006

An alternative to blood transfusion, based on oxygen‐carrying solutions, has been sought for over a century. The present ‘first‐generation’ haemoglobin‐products were based on observations that crosslinking with, for example, glutaraldehyde, overcame subunit dissociation and renal toxicity. Experience with these solutions has shown that they can be vasoactive, sometimes increasing blood pressure, sometimes decreasing tissue perfusion and sometimes both. Clinical trials have been disappointing because of unexpected toxicity. The ‘second‐generation’ products are based on a better understanding of the mechanisms of this vasoconstriction. Such products may seem counterintuitive by traditional standards, but it is hoped that they will be less toxic, more beneficial to patients, and more economical to produce.
Increased serum level of vascular endothelial growth factor in Mycobacterium avium complex infection
Authors: NISHIGAKI Yutaka , FUJIUCHI Satoru , FUJITA Yuka , YAMAZAKI Yasuhiro , SATO Maki , YAMAMOTO Yasushi , TAKEDA Akinori , FUJIKANE Toshiaki , SHIMIZU Tetsuo , KIKUCHI Kenjiro
Published: May 2006

Objective:  Pulmonary infection caused by Mycobacterium avium complex (MAC) is one of the granulomatous diseases which are associated with the expression of vascular endothelial growth factor (VEGF). The aim of the present study was to clarify the association of VEGF with the pathogenesis of MAC infection.

Methodology:  The serum VEGF levels in 46 patients with pulmonary MAC infection were compared with those in 16 normal control subjects. Pulmonary lesions were evaluated using chest CT. In 20 patients, after treatment, serum VEGF levels were measured and chest CT performed again to evaluate pulmonary response to treatment.

Results:  Infected patients had higher serum VEGF levels than controls (435.2 ± 29.1 vs. 167.0 ± 10.6 pg/mL, P < 0.0001), and serum VEGF level correlated with the extent of disease. The serum VEGF levels in 14 patients who underwent treatment and exhibited an improvement in their pulmonary lesions decreased significantly compared with the results pretreatment (509.0 ± 60.7 vs. 303.6 ± 65.3 pg/mL, P = 0.0092). In infected patients, alveolar macrophages, epithelioid cells and multinucleated giant cells exhibited VEGF overexpression on immunohistochemical staining.

Conclusions:  This study suggests that VEGF may be associated with the pathogenesis of pulmonary MAC infection. Additionally, serum VEGF levels may be a useful surrogate marker for evaluating the extent of disease and of the response to treatment.
[125I]Iodomethyllycaconitine binds to α7 nicotinic acetylcholine receptors in monkey brain
Authors: Kulak Jennifer M. , Ivy Carroll F. , Schneider Jay S.
Published: May 2006

We examined the binding of the novel nicotinic acetylcholine receptor (nAChR) ligand [125I]iodomethyllycaconitine (iodoMLA) in the brains ofM. cynomologous(macaque) monkeys. [125I]iodoMLA bound throughout the brain with the greatest density in the thalamus and moderate intensity in the basal ganglia and cortical regions. The Kd and Bmax in whole brain tissue were similar whether 1 mmnicotine (Kd 33.25 ± 15.17 nm, Bmax 5.80 ± 1.06 fmol/mg) or 2 µmof the α7‐selective antagonist α‐bungarotoxin (Kd 46.12 ± 18.45 nm, Bmax 6.30 ± 1.06 fmol/mg) was used for nonspecific binding. The subtype‐selectivity of this ligand was further studied with competition binding studies using nicotine, α‐bungarotoxin and noniodinated MLA. Each ligand completely inhibited [125I]iodoMLA binding throughout the monkey brain, with Ki values of 2.23 ± 0.85 µmfor nicotine, 2.72 ± 1.71 nmfor α‐bungarotoxin and 1.83 ± 0.35 nmMLA in the caudate and 2.03 ± 1.14 µm, 2.65 ± 0.86 nmand 3.32 ± 0.71 nm, respectively, in the putamen. The α3β2/α6*‐selective antagonist α‐conotoxin MII failed to inhibit [125I]iodoMLA binding in any brain region. In monkeys with cognitive deficits resulting from 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine administration, [125I]iodoMLA binding was significantly increased in the striatum, similar to results previously observed for [125I]α‐bungarotoxin. These results suggest that, under the present experimental conditions, [125I]iodoMLA was selective for α7‐containing nAChRs and did not bind to α6‐containing nAChRs. This radioligand may be a useful tool for selectively imaging α7‐containing nAChRsin vivo.
Applying Meta‐theory to Achieve Generalisability and Precision in Personality Science
Authors: Shoda Yuichi , Mischel Walter
Published: May 2006

In contrast to traditional theories of personality, the CAPS perspective is a meta‐theory that is deliberately “content‐free”. The generalisability of the theory depends on how widely its basic, common principles and methods can be applied to identify the constructs (e.g. situation‐specific encodings, beliefs, values, etc.) relevant to a given domain of behavior and situations. In this commentary we will discuss how the target article illustrates the use of the CAPS meta‐theory for developing domain‐specific content‐full models for smoking cessation, psychopathology, and organisational behavior.
Lessons from the tropics for a global geomorphology
Authors: Thomas Michael F.
Published: May 2006

Historically, geomorphologists have applied uniformitarian principles based on a temperate normality to all water‐worn landscapes. Isolation of tropical landforms within formal morphogenetic regions, which arose during the early history of the subject, has persisted. However, in a global geomorphology, plate tectonic motion, Milankovich cycles of climate change and invasive weather systems all render fixed climatic boundaries meaningless and, on every timescale of enquiry, interaction of the tropics with extra‐tropical regions is fundamental. In tropical regions, the continuity of weathering processes through geologic time emphasizes their contemporary relevance and, with knowledge of Quaternary climate changes, increases understanding of the nature of landscape sensitivity and instability and fluvial sedimentation on millennial timescales. Examples are illustrated from northeast Queensland, Australia and northwest Kalimantan, Indonesia. Global concerns centred on hazards and resources need to be addressed through a reciprocal exchange of ideas involving greater focus on tropical areas.
Effect of Environmental Factors and Gender on the Heritability of Bone Mineral Density and Bone Size
Authors: Ng M. Y. M. , Sham P. C. , Paterson A. D. , Chan V. , Kung A. W. C.
Published: May 2006

Bone mineral density (BMD), a risk factor for osteoporosis, is believed to be under genetic control. The effect of environmental factors and gender on the heritability of BMD and bone size is ill‐defined. In this study, heritability estimates (h2) were determined in 3,320 southern Chinese subjects from 1,019 families using the variance components model. The h2 for age, weight and height‐adjusted BMD was 0.63–0.71 for females, and 0.74–0.79 for males; and for bone size, 0.44–0.64 for females and 0.32–0.86 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking and alcohol consumption altered the h2 differently in males and females. The proportion of variance in BMD and bone size explained by all covariates varied between skeletal sites, but was consistently greater in females than males. A significant gender difference was observed in the genetic variance of BMD and bone size at the hip but not the spine. In conclusion, a gender difference was observed in the degree of heritability of BMD and bone size at specific skeletal sites. Environmental influences contributed variably at different sites in the two sexes.
Central Administration of an Opiate Antagonist Decreases Oral Ethanol Self‐Administration in Rats
Authors: Heyser Charles J. , Roberts Amanda J. , Schulteis Gery , Koob George F.
Published: May 2006

Background: Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self‐administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects of drugs of abuse.

Methods: Male Wistar rats were trained in a limited‐access paradigm (30 min/day) to respond for ethanol (10% w/v) or water in a two‐lever free‐choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, animals were implanted stereotaxically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0‐2000 ng).

Results: Injections of methylnaloxonium into the amygdala significantly reduced responding for ethanol at doses of 250–500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500–1000 ng, whereas higher doses were needed ICV.

Conclusions: These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self‐administration.
Evaluation of the Yale‐Brown Obsessive Compulsive Scale (YBOCS‐hd) for Heavy Drinking With Mild to Moderately Dependent Alcohol Abusers
Authors: Fedoroff Ingrid , Sobell Linda C. , Agrawal Sangeeta , Sobell Mark B. , Gavin Douglas R.
Published: May 2006

Background: Many similarities have been noted between urges and desires to drink heavily and obsessive‐compulsive disorders (OCD). Based on such similarities, Modell et al. (1992) developed the Yale‐Brown Obsessive Compulsive Scale for heavy drinking (YBOCS‐hd), a modified version of YBOCS, to assess obsessions and compulsions related to heavy drinking. Evaluation of the YBOCS‐hd has been limited to more severely dependent alcohol abusers.

Methods: The present study used a self‐administered version of the YBOCS‐hd to evaluate (1) the severity of drinking‐related obsessive compulsive symptoms with mild to moderately dependent alcohol abusers (problem drinkers), and (2) whether end‐of‐treatment changes in YBOCS‐hd scores would be related to within‐treatment functioning.

Results: Results indicated that problem drinkers have lower alcohol‐related Obsessive and Compulsive subscale scores than did more severely dependent drinkers, but higher scores than did non‐problem drinkers, supporting the construct validity of the YBOCS‐hd. In addition, at the end of treatment, the YBOCS‐hd scores of alcohol abusers who drank at low‐risk levels during treatment were significantly lower than the scores of those who drank at high‐risk levels. Lastly, exploratory factor analysis did not provide support for the two purported YBOCS‐hd subscales (Obsessive, Compulsive). Instead, the analysis yielded a single general factor and a second factor that contained two questions measuring heavy drinking.

Conclusions: Despite the fact that total YBOCS‐hd scores covaried with drinking, neither the total YBOCS‐hd pretreatment score nor the two subscale scores predicted functioning at the end of treatment. The present results call into question the utility of the YBOCS‐hd, because a single item measuring the heaviness of drinking was as useful as the total YBOCS‐hd and its two subscales in relating changes during treatment to end‐of‐treatment functioning for problem drinkers. However, although the YBOCS‐hd does not predict changes in drinking, it may have value as an indirect measure of drinking in situations where direct measurement of alcohol consumption is undesirable (i.e., direct measurement might be reactive). Because the present findings are derived from problem drinkers, further research is needed to confirm the factor structure of the YBOCS‐hd with clients who represent a broader range of alcohol problem severity.
Suppression of Mismatch Negativity by Backward Masking Predicts Impaired Working‐Memory Performance in Alcoholics
Authors: Ahveninen Jyrki , Jääskeläinen Iiro P. , Pekkonen Eero , Hallberg Anja , Hietanen Marja , Mäkelä Rauno , Näätänen Risto , Sillanaukee Pekka
Published: May 2006

Background: Pronounced disruption of memory traces by subsequent distractors may result in impaired behavioral memory performance in alcoholics.

Methods: This hypothesis was investigated with an electrophysiological index of auditory sensory‐memory traces, mismatch negativity, a preattentive event‐related potential component elicited by a “deviant” tone within a train of “standard” tones.

Results: Inserting a masking stimulus after these tones abolished mismatch negativity in alcoholics (DSM‐IV) but not in social‐drinker controls. This effect predicted working‐memory impairment in alcoholics, and correlated significantly with self‐reported alcohol consumption of the subjects. Furthermore, the backward‐masking mismatch negativity paradigm detected sensory‐memory impairment in 9 of 20 alcoholics (sensitivity 45%), whereas all 20 social drinkers were unimpaired (specificity 100%).

Conclusions: Vulnerability to memory trace disruption by shortly following sounds may be one of the factors contributing to behavioral memory dysfunction in alcoholics. The present result may provide an objective neurophysiological tool for investigation of alcohol‐induced and other degenerative brain disorders.
Effect of Cigarette Smoking on ACTH/Cortisol Secretion in Alcoholics After Short‐ and Medium‐Term Abstinence
Authors: Coiro V. , Vescovi P. P.
Published: May 2006

Background: To gain a better insight into the alterations of the hypothalamic‐pituitary‐adrenal axis in alcoholism, we evaluated the ACTH response to nicotine inhaled from cigarette smoking (two nonfilter cigarettes in succession within 10 min) in nine nonalcoholic men and nine age‐ and weight‐matched alcoholic men who had been addicted to alcohol for at least 8 years. All subjects were regular cigarette smokers.

Methods: Alcoholic men were tested after 2 weeks of abstinence, when the possible interferences because of alcohol assumption or the acute withdrawal period had completely ceased, and again after 12 weeks of abstinence.

Results: At both 2 and 12 weeks of abstinence, basal plasma ACTH and Cortisol levels were not significantly different in the alcoholic men from those observed in the control group. In the control group subjects, cigarette smoking induced a striking increase in the circulating concentrations of ACTH and Cortisol, with peak responses 1.4 and 1.5 times higher than baseline at 20 and 30 min, respectively. In contrast, no significant ACTH/cortisol increase was observed in alcoholic subjects at any time after cigarette smoking in any test.

Conclusion: These data suggest that alterations of nicotinic cholinergic transmission occur in the control of ACTH secretion in the alcholic men, providing further evidence of modification of the hypothalamic‐pituitary‐adrenal axis in alcoholism.
Nitric Oxide Dependent Ethanol Stimulation of Ciliary Motility Is Linked to cAMP‐Dependent Protein Kinase (PKA) Activation in Bovine Bronchial Epithelium
Authors: Sisson Joseph H. , May Kathy , Wyatt Todd A.
Published: May 2006

Background:The first line of protection in the lung from the outside environment is provided by the mucociliary apparatus, which continually clears the airways of inhaled microorganisms, dust, and debris. Because alcohol is known to impair airway host defenses, we have examined the effects of ethanol on mucociliary function. In earlier studies, we found that ethanol rapidly and transiently stimulates ciliary motility through a nitric oxide‐dependent mechanism. Because many agonists stimulate ciliary motility through activation of cyclic nucleotide‐dependent protein kinases, we hypothesized that ethanol stimulates ciliary motility by activating protein kinases.

Methods:Protein kinase activity and ciliary beat frequency (CBF) were assayed in primary cultures of bovine bronchial epithelial cells after exposure to ethanol.

Results:Ethanol markedly activated cyclic adenosine monophosphate (cAMP)‐dependent protein kinase [protein kinase A (PKA)] at biologically relevant concentrations (20‐100 mM), with activation detectable after 15 min and persisting up to 4 hr. Ethanol's PKA activation was blocked by nitric oxide synthase inhibitors, indicating a nitric oxide‐dependent pathway, and was also specifically blocked by PKA inhibitors. Ethanol did not directly activate cyclic guanosine monophosphate (cGMP)‐dependent protein kinase [protein kinase G (PKG)] in bovine bronchial epithelial cells, but inhibitors of PKG attenuated PKA activation, suggesting a link between PKA activation and PKG activation during ethanol exposure. CBF increased in parallel to PKA activation, suggesting tight coupling between stimulated CBF and PKA activation.

Conclusion:We conclude that ethanol stimulates CBF through activating PKA in bovine bronchial epithelial cells and wc suggest a cooperative mechanism involving PKA and nitric oxide.
China's Energy in Transition: Regional and Global Implications
Authors: CHU Tianshu , FESHARAKI Fereidun , WU Kang
Published: May 2006

China is the largest energy user in Asia and the second largest in the world after the US. This paper documents substantial changes of the structure of China's energy use over the past decades. It explores the puzzling phenomena of China's low gross domestic product elasticity of energy consumption. Econometric analysis applying the AutoRegressive Integrated Moving Average model finds that factors such as institutional reforms and structural change can account for a substantial fraction of the downward impacts on the elasticity level. The paper also studies the future energy growth and energy security issues in China, and examines the regional and global impacts of China's rapidly growing energy consumption.
Stroke among male professional drivers in Denmark, 1994–2003
Authors: Tüchsen F , Hannerz H , Roepstorff C , Krause N
Published: May 2006

Objectives:(1) To estimate the relative risk of stroke among various groups of professional drivers; (2) to determine if any excess risk should be attributed to infarction or haemorrhage; (3) to estimate the relative risk ratio for stroke among professional drivers living in Greater Copenhagen compared to those living outside the metropolis.

Methods:A cohort of 6285 bus drivers, 4204 car, taxi, and van drivers, and 25 879 heavy truck and lorry drivers were followed up for hospital admission due to stroke and sub-diagnoses in the period 1994–2003. Using hospital admission for all economically active men as the standard, the standardised hospitalisation ratios (SHR) were calculated, taking age and county into consideration.

Results:There was a high SHR for stroke among all groups of professional drivers (SHR = 132; 95% CI 121–141). Among car, taxi, and van drivers the SHR was 157 (95% CI 132–189), among bus drivers it was 139 (95% CI 119–163), and among heavy truck and lorry drivers it was 124 (95% CI 113–136). The excess risk for all groups of professional drivers was highest for cerebrovascular infarction (SHR = 139; 95% CI 124–155) and lowest for non-traumatic intracranial haemorrhage (SHR = 113; 95% CI 96–133). The excess risks for all groups were significantly higher for cerebrovascular infarction than for non-traumatic intracranial haemorrhage (relative risk ratio (RRR) 1.23; 95% CI 1.01–1.51). The RRR of stroke among drivers in the metropolitan area compared to rural areas was 1.13 (95% CI 0.94–1.36). The RRR for stroke among car, taxi, and van drivers compared to drivers of heavy trucks and of lorries was 1.28 (95% CI 1.03–1.57).

Conclusion:All groups of professional drivers are at increased risk of stroke. The excess risk is more due to cerebral infarctions than to non-traumatic intracranial haemorrhage. The risk of stroke is higher among drivers carrying passengers than among drivers carrying goods.
Increased glomerular permeability to negatively charged Ficoll relative to neutral Ficoll in rats
Authors: Asgeirsson Daniel , Venturoli Daniele , Rippe Bengt , Rippe Catarina
Published: May 2006

It is established that the glomerular filter sieves macromolecules based on their size, shape, and charge. Anionic proteins are thus retarded compared with their neutral or cationic counterparts. However, recent studies have indicated that charge effects are small, or even “anomalous,” for polysaccharides. We therefore investigated the impact of charge on the glomerular permeability to polysaccharides by comparing sieving coefficients (θ; primary urine-to-plasma concentration ratio) for negatively charged, carboxymethylated (CM) FITC-Ficoll and FITC-dextran with their neutral counterparts. For these probes, θ were determined in anesthetized Wistar rats [269 ± 2.7 g (±SE; n = 36)], whose ureters were cannulated for urine sampling. The glomerular filtration rate was assessed using FITC-inulin. Polysaccharides were constantly infused, and after equilibration, urine was collected and a midpoint plasma sample was taken. Size and concentration determinations of the FITC-labeled polysaccharides were achieved by size-exclusion HPLC (HPSEC). For CM-Ficoll, θ was significantly increased (32 times at 55 Å) compared with that of uncharged Ficoll. A small increase in θ for CM-dextran compared with neutral dextran was also observed (1.8 times at 55 Å). In conclusion, negatively charged Ficoll relative to neutral Ficoll was found to be markedly hyperpermeable across the glomerular filter. Furthermore, negatively charged Ficoll was observed to be larger on HPSEC compared with its neutral counterpart of the same molecular weight. It is proposed that the introduction of negative charges in the “dendrimeric,” cross-linked Ficoll molecule may alter its configuration, so as to make it more extended, and conceivably, more flexible, thereby increasing its glomerular permeability.
Disruption of Coherent Oscillations in Inhibitory Networks With Anesthetics: Role of GABAA Receptor Desensitization
Authors: Baker Pamela M. , Pennefather Peter S. , Orser Beverley A. , Skinner Frances K.
Published: May 2006

The effect of anesthetic drugs at central synapses can be described quantitatively by developing kinetic models of ligand-gated ion channels. Experiments have shown that the hypnotic propofol and the sedative benzodiazepine midazolam have similar effects on single inhibitory postsynaptic potentials (IPSPs) but very different effects on slow desensitization that are not revealed by examining single responses. Synchronous oscillatory activity in networks of interneurons connected by inhibitory synapses has been implicated in many hippocampal functions, and differences in the kinetics of the GABAergic response observed with anesthetics can affect this activity. Thus we have examined the effect of propofol and midazolam-enhanced IPSPs using mathematical models of self-inhibited one- and two-cell inhibitory networks. A detailed kinetic model of the GABAA channel incorporating receptor desensitization is used at synapses in our models. The most dramatic effect of propofol is the modulation of slow desensitization. This is only revealed when the network is driven at frequencies that are thought to be relevant to cognitive tasks performed in the hippocampus. The level of desensitization at synapses with propofol is significantly reduced compared to control synapses. In contrast, midazolam increases macroscopic desensitization at network synapses by altering receptor affinity without concurrently modifying desensitization rates. These differences in gating between the two drugs are shown to alter network activity in stereotypically different ways. Specifically, propofol dramatically increases the amount of excitatory drive necessary for synchronized behavior relative to control, which is not the case for midazolam. Moreover, the range of parameters for which synchrony occurs is larger for propofol but smaller for midazolam, relative to control. This is an important first step in linking alterations in channel kinetics with behavioral changes.
Multiple Features of Motor-Unit Activity Influence Force Fluctuations During Isometric Contractions
Authors: Taylor Anna M. , Christou Evangelos A. , Enoka Roger M.
Published: May 2006

To identify the mechanisms responsible for the fluctuations in force that occur during voluntary contractions, experimental measurements were compared with simulated forces in the time and frequency domains at contraction intensities that ranged from 2 to 98% of the maximum voluntary contraction (MVC). The abduction force exerted by the index finger due to an isometric contraction of the first dorsal interosseus muscle was measured in 10 young adults. Force was simulated with computer models of motor-unit recruitment and rate coding for a population of 120 motor units. The models varied recruitment and rate-coding properties of the motor units and the activation pattern of the motor-unit population. The main finding was that the experimental observations of a minimum in the coefficient of variation (CV) for force (1.7%) at approximately 30% MVC and a plateau at higher forces could not be replicated by any of the models. The model that increased the level of short-term synchrony with excitatory drive provided the closest fit to the experimentally observed relation between the CV for force and the mean force. In addition, the results for the synchronization model extended previous modeling efforts to show that the effect of synchronization is independent from that of discharge-rate variability. Most of the power in the force power spectra for the models was contained in the frequency bins below 5 Hz. Only a model that included a low-frequency oscillation in excitation, however, could approximate the experimental finding of peak power at a frequency below 2 Hz: 38% of total power at 0.99 Hz and 43% at 1.37 Hz, respectively. In contrast to the experimental power spectra, all model spectra included a second peak at a higher frequency. The secondary peak was less prominent in the synchronization model because of greater variability in discharge rate. These results indicate that the variation in force fluctuations across the entire operating range of the muscle cannot be explained by a single mechanism that influences the output of the motor-unit population.