bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and environmental influences on the association between smoking and panic attacks in females: a population-based twin study
Authors: REICHBORN-KJENNERUD TED , RØYSAMB ESPEN , TAMBS KRISTIAN , TORGERSEN SVENN , KRINGLEN EINAR , MAGNUS PER , HARRIS JENNIFER R.
Published: October 2004

Background. Clinical and epidemiological studies have reported an association between lifetime cigarette-smoking and panic attacks. Several explanations for this relationship have been proposed, mostly focusing on direct causal pathways. The objective of this study was to investigate a hypothesis of shared vulnerability by examining whether panic attacks and cigarette-smoking share genetic or environmental liability factors.

Method. Questionnaire data on 3172 female–female twins (1409 complete pairs), aged 18–31 years, from a population-based Norwegian twin registry, were used to calculate the correlation between genetic factors and the correlation between environmental factors that influence lifetime measures of panic attacks and daily smoking.

Results. The best-fitting biometrical twin model suggested that genetic factors influencing panic and smoking were uncorrelated. Shared or familial environmental factors were perfectly correlated, and accounted for 75% of the association between the phenotypes. The correlation between individual environmental factors influencing the phenotypes was 0·25 (0·07–0·44). In the full model, the genetic correlation was 0·17 (0·00–1·00), and genetic and shared environmental factors respectively accounted for 18% and 61% of the co-variance between panic and smoking.

Conclusion. The results suggest that panic attacks and lifetime smoking have few or no genetic liability factors in common. The shared environmental factors that influence the two phenotypes are identical. Liability to panic attacks in females appears to be more influenced by shared environmental factors than previously indicated by univariate studies.
A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence
Authors: MAES HERMINE H. , SULLIVAN PATRICK F. , BULIK CYNTHIA M. , NEALE MICHAEL C. , PRESCOTT CAROL A. , EAVES LINDON J. , KENDLER KENNETH S.
Published: October 2004

Background. Numerous twin studies have reported significant genetic contributions to the variability of tobacco initiation (TI), while fewer studies have shown similar results for the persistence of smoking behavior, or nicotine dependence (ND). As the development of ND requires regular tobacco use (RTU) which in turn requires TI, a conditional approach is necessary.

Method. We used structural equation modeling of multi-step conditional processes to examine the relationship between genetic and environmental risk factors for TI, RTU and ND. The tobacco variables were assessed by personal interview in female, male and opposite-sex twin pairs from the population-based Virginia Twin Registry.

Results. The results suggested that the liabilities to TI, RTU and ND were correlated. Over 80% of the variance in liability to TI and RTU were shared, and a smaller proportion was shared between RTU and ND. The heritabilities were estimated at 75%, 80% and 60% respectively for TI, RTU and ND. The variance specific to liability to RTU was entirely accounted for by additive genetic factors. Only a modest part of the heritability in liability of ND was due to genetic factors specific to ND. Shared environmental factors were not significant. No sex differences were found for the sources of variation or causal paths, but prevalences were significantly greater in males versus females.

Conclusions. This study showed significant overlap in the contribution of genetic factors to individual differences in TI, RTU and ND. Furthermore, there was evidence for significant additional genetic factors specific to RTU and ND.
Level of family dysfunction and genetic influences on smoking in women
Authors: KENDLER KENNETH S. , AGGEN STEVEN H. , PRESCOTT CAROL A. , JACOBSON KRISTEN C. , NEALE MICHAEL C.
Published: October 2004

Background. An adoption study of alcoholism suggests that in women, the impact of genetic risk factors become greater in the presence of conflict in the family of origin. Is the same true for cigarette smoking (CS)?

Method. We obtained, in a sample of 1676 twins from female–female twin pairs from a population-based register, a measure of maximum lifetime CS (divided into six ordinal categories) and family dysfunction (FD) assessed as the mean report of up to four informants (twin, co-twin, mother, father). Statistical analysis was conducted by traditional regression analysis and a moderator structural equation twin model using the computer program Mx.

Results. With increasing levels of FD, maximum CS increased substantially while correlations for CS in monozygotic (MZ) and dizygotic (DZ) twins decreased modestly. Regression analyses demonstrated reduced twin-pair resemblance for CS with increasing levels of FD. The best-fit structural equation model found high levels of heritability for CS and no evidence for a role of shared environment. With increasing levels of FD, the proportion of variance in CS due to genetic factors (i.e. heritability) decreased while that due to unique environmental effects increased.

Conclusions. Several different statistical methods suggested that, contrary to prediction, heritability of CS decreased rather than increased with higher levels of dysfunction in the family of origin. The hypothesis that genetic effects for psychiatric and drug-use disorders become stronger in more adverse environments is not universally true.
Expanding our understanding of the relationship between negative life events and depressive symptoms in black and white adolescent girls
Authors: FRANKO DEBRA L. , STRIEGEL-MOORE RUTH H. , BROWN KATHLEEN M. , BARTON BRUCE A. , McMAHON ROBERT P. , SCHREIBER GEORGE B. , CRAWFORD PATRICIA B. , DANIELS STEPHEN R.
Published: October 2004

Background. Little is known about the extent to which negative life events predict depressive symptoms in ethnically diverse groups or whether this relationship is proximal or enduring.

Method. The relationship between negative life events in adolescence and depressive symptoms in young adulthood was studied in a sample of over 1300 black and white female adolescents. Five domains of life events were assessed at age 16 years and depressive symptoms were measured at age 18 and again at age 21 years. Questions of interest included whether the association continued over time and whether there were specific domains of life events that predicted symptoms better than others.

Results. The total number of negative life events at time 1 predicted depressive symptoms at both time 2 and time 3. Interpersonal loss events and other adversities, however, predicted depressive symptoms only at time 2, whereas at time 3, only interpersonal trauma was a significant predictor. No ethnic differences were found, indicating that the relationship between life events and depressive symptoms appears to be similar for black and white adolescent girls.

Conclusions. The results suggest that negative life events and some specific type of stressors increase the likelihood of the onset of depression symptoms in future years, for both black and white girls. Early preventive efforts should be directed at adolescents who experience loss due to death of a significant other, traumatic events, and psychosocial adversities to forestall the development of depressive symptoms.
Scripture, revelation and Platonism in C. S. Lewis
Authors: Walker Andrew
Published: October 2004

Noting that C. S. Lewis's writings do not contain a systematic statement of his understanding of the relationship between scripture and revelation, this essay exposes the literary, theological and philosophical undergirding of his approach to scripture, which was neither fundamentalist nor modernist. It then outlines his treatment of six ‘modes’ of revelation: five general and incomplete (the numinous, the notion of Sehnsucht, conscience/the moral law, the election of Israel, pagan myths), the sixth particular and perfect – Jesus Christ. After considering Lewis's notion of ‘transposition’ and delineating the trajectory of his philosophical idealism, the essay contends that Lewis's tendency to Platonise reality leads him to articulate some unfortunate and unsatisfactory theological expressions.
Wisdom: the Queen of Heaven
Authors: Barker Margaret
Published: October 2004

The female deity of ancient Israel should be studied using the same methods as for the male. Priority should be given to written evidence, there should be recognition of a variety of names and titles for the one figure in both singular and plural forms, and it must be admitted that as conceptions of the male deity moved away from anthropomorphism, it is unlikely that the female deity would have had an exactly opposite fate. Evidence from the Hebrew scriptures, the Enochic writings, archaeology and early Christian tradition all suggest that Wisdom was the name by which the pre-Josianic female deity was best known.
The crucified Christ as the motherly God: the theology of Julian of Norwich
Authors: Dearborn Kerry
Published: October 2004

Is there valid justification for affirming the motherliness of God while holding fast to the cross and to the Judeo-Christian heritage? Some feminists view the God of Abraham and Jesus as so closely linked with patriarchy and abuse that they reject this God as hopelessly male. Other theologians adhere to an exclusive emphasis on God as Father, and regard motherly appellations of God as distortions of biblical faith. Can the crucifixion and the atonement be seen in terms that are affirming of that which is female, yet remain grounded in the biblical texts and traditions? This article focuses on the theology of Julian of Norwich, whose meditations on the cross provide a middle way of affirming both the motherly nature of God and biblical revelation and tradition.
The angel of the great counsel of God and the Christology of the Scots Confession of 1560
Authors: Owen John Michael
Published: October 2004

The Scots Confession announces the incarnate Son as the ‘angel of the great counsel of God’. Derived from Isa 9:6(5) LXX, that title has come through a tradition traceable through Justin, Irenaeus, Athanasius, Augustine and Calvin. It designates Jesus in his teaching ministry and prophetic office as revealer of God's saving purpose carried out in him and expresses both connection and distinction between God's eternal Wisdom and its incarnation. Parallels in Calvin's polemic against Osiander bring out the Confession's emphasis on the saving and revelatory significance of Jesu' humanity and his being both communicator and content of the divine counsel.
Community, character, and gender: women and the work of Stanley Hauerwas
Authors: Murphy Debra Dean
Published: October 2004

This essay explores the intersection between feminism and the work of Stanley Hauerwas. The recent critiques of Hauerwas's writings by Gloria Albrecht and Linda Woodhead are examined and a general assessment of the relationship between feminist theology (in its various guises) and Hauerwas's work is offered. It is suggested that the intersection of Hauerwas's theology with some strands of feminism reveals some surprisingly similar theological convictions and faith commitments, and that these areas of common concern offer unique opportunities for mutual engagement and enhancement.
A response to Liz Clark
Authors: Drake H. A.
Published: October 2004

Elizabeth Clark was characteristically generous and incisive in her comments. She asks six questions, which I will paraphrase as follows: (1) How can we know Constantine's intentions? (2) Did ‘pagan monotheism’ have a broad enough appeal to create the type of constituency Constantine would have needed, and (3) even if it did, would not the turn from ‘cultic practice’ to ‘a system of belief’ – whether pagan or Christian – still have resulted in ‘intolerance and its political analogue, compulsion’? (4) Do I overrate the impact of Julian? (5) ‘Where are the Jews in this discussion?’ (6) Can metaphors based on modern political language and a public policy model be applied to this period without distorting the subject?
RELIGIOUS CEREMONIAL AT THE TUDOR COURT: EXTRACTS FROM ROYAL HOUSEHOLD REGULATIONS
Authors: Kisby Fiona
Published: October 2004

Acknowledgements

Editorial Practice

Introduction

Inventory of BL, Additional MS 71009

Extracts from Royal Household regulations […]
MEMOIRES ET PROCEDURES DE MA NEGOCIATION EN ANGLETERRE (8 OCTOBER 1582–8 OCTOBER 1583) BY JEAN MALLIET, COUNCILLOR OF GENEVA
Authors: Adams Simon , Greengrass Mark
Published: October 2004

Acknowledgements

Editorial practice

Introduction

Mémoires et procédures de ma negotiation […]
A trajectory‐based study of the tropical tropopause region
Authors: Bonazzola M. , Haynes P. H.
Published: October 2004

Large ensembles of 90‐day backward trajectory calculations from the tropical lower stratosphere are performed for Northern Hemisphere (NH) winters 1997–1998 and 1998–1999 and summer 1999 on the basis of European Center for Medium‐Range Weather Forecasts operational analysis data. The calculated trajectories are analyzed to determine patterns of transport and encountered temperatures and implications for lower stratospheric water vapor. For each set of back‐trajectories, a troposphere‐to‐stratosphere (TS) ensemble, originating below 355 K, is identified. Trajectories in the TS ensemble sample the coldest regions of the tropical tropopause region very efficiently. Corresponding water vapor concentrations are calculated using two simple dehydration models, one (model 1) assuming instantaneous dehydration and the other (model 2) taking some account of time delays associated with microphysical processes. Model 1 predicts average concentrations for the TS ensembles of 1.5 and 2.0 ppmv in the two NH winters and 3.8 ppmv in NH summer. Model 2 predicts concentrations that are about 0.5 ppmv larger. The effect of temperature variability along the trajectories is considered and is shown to arise primarily through horizontal advection through strong gradients rather than through temporal variability. A quantitative method is described to assess the efficiency of sampling of cold regions, the roles played by different transport processes, and differences between seasons or years. Both vertical transport (the “stratospheric fountain” effect) and horizontal transport are shown to play important roles in dehydration, with the former more important in NH winter and the latter more important in NH summer. Differences in predicted water vapor between NH winter 1997–1998 (El Niño) and 1998–1999 (La Niña) are due to the warmer region of coldest temperatures in 1997–1998 than in 1998–1999 and to the less efficient sampling of cold temperatures by both horizontal and vertical circulations during the former.
Spatiotemporal patterns of cropland area and net primary production in the central United States estimated from USDA agricultural information
Authors: Hicke Jeffrey A. , Lobell David B.
Published: October 2004

The central United States, which is dominated by agriculture, has been selected as the first North American Carbon Program intensive campaign. Data sets that describe spatiotemporal variability in carbon fluxes are needed to support this campaign. Here we report the behavior of county cropland net primary production (NPP) in the first intensive region derived using USDA information together with crop‐specific parameters that convert agronomic data into carbon fluxes. Total cropland area in the eight‐state region was ∼550,000 km2 (40% of total area), with some interannual variability but no temporal trend from 1972 to 2001. Regional production (P) was 0.3 Pg C yr−1 in the late 1990s, roughly 64% of the total US crop production. P was highest in the central counties (>1.2 Tg C yr−1). In contrast to area, both NPP (flux per unit area) and P (spatially aggregated flux) increased during the study period (46 and 51%, respectively). Corn was the dominant crop type grown in the region, contributing 58% of the total production, with soybeans second most productive but substantially less (20%) despite similar harvested area. Maximum year‐to‐year variability in P was high, generally greater than 30% for most counties, though exceeding 80% for some counties.
Estimation of ocean subsurface thermal structure from surface parameters: A neural network approach
Authors: Ali M. M. , Swain D. , Weller R. A.
Published: October 2004

Satellite remote sensing provides diverse and useful ocean surface observations. It is of interest to determine if such surface observations can be used to infer information about the vertical structure of the ocean's interior, like that of temperature profiles. Earlier studies used either sea surface temperature or dynamic height/sea surface height to infer the subsurface temperature profiles. In this study we have used neural network approach to estimate the temperature structure from sea surface temperature, sea surface height, wind stress, net radiation, and net heat flux, available from an Arabian Sea mooring from October 1994 to October 1995, deployed by the Woods Hole Oceanographic Institution. On the average, 50% of the estimations are within an error of ±0.5°C and 90% within ±1.0°C. The average RMS error between the estimated temperature profiles and in situ observations is 0.584°C with a depth‐wise average correlation coefficient of 0.92.
Seasonal variations in N and O isotopes of nitrate in snow at Summit, Greenland: Implications for the study of nitrate in snow and ice cores
Authors: Hastings Meredith G. , Steig E. J. , Sigman D. M.
Published: October 2004

Nitrogen and oxygen isotopes of NO3− have been measured in snow and firn from Summit, Greenland. The 15N/14N and 18O/16O ratios of NO3− in recently fallen snow are similar to those of surface snow. Diurnal variation is observed in 15N/14N of NO3−, and possibly 18O/16O, suggesting fractionating loss of NO3− from snow during the day, which is subsequently recovered at night. A larger seasonal variation is observed, with higher 15N/14N and lower 18O/16O of NO3− in summer than winter, which cannot be explained by postdepositional fractionation. The generally high 18O/16O of NO3− in Greenland snow (δ18O versus VSMOW = 65.2 to 79.6‰) indicates that oxygen atoms from ozone have been incorporated into NOx that was subsequently deposited as HNO3. The lower mean δ18O of NO3− in summer snow relative to winter (68.9‰ in summer 2000 and 70.5‰ in summer 2001 versus 77.5‰ in winter 2000–01) is a result of summertime HNO3 production via NO2 reaction with hydroxyl radical (OH), which dilutes the high δ18O imparted on NO2 from ozone. The higher mean 15N/14N of NO3− observed in snow from spring (δ15N versus air N2 = +5.9‰ in 2000 and −1.4‰ in 2001) and summer (+0.1‰ in 2000 and −0.8‰ in 2001) than fall (−9.2‰ in 2000) and winter (−10.0‰ in 2000–01) is more difficult to explain with seasonal photochemistry, given current knowledge. The seasonal 15N/14N change may reflect NOx sources, with a greater fall and wintertime contribution from fossil fuel emissions relative to other inputs of NOx (i.e., biogenic soil emissions, biomass burning, and lightning).
New particle formation observed in the tropical/subtropical cirrus clouds
Authors: Lee S.‐H. , Wilson J. C. , Baumgardner D. , Herman R. L. , Weinstock E. M. , LaFleur B. G. , Kok G. , Anderson B. , Lawson P. , Baker B. , Strawa A. , Pittman J. V. , Reeves J. M. , Bui T. P.
Published: October 2004

Previous studies show that new particle formation takes place in the outflows of marine stratus and cumulus clouds. Here we show measurements of high concentrations of ultrafine particles, diameters (Dp) from 4 to 9 nm (N4–9), in interstitial cloud aerosol. These ultrafine particles indicate that in situ new particle formation occurs interstitially in cirrus clouds. Measurements were made at altitudes from 7 to 16 km over Florida with instruments on the WB‐57F aircraft during Cirrus Regional Study of Tropical Anvils and Cirrus Layers‐Florida Area Cirrus Experiments (CRYSTAL‐FACE) in July 2002. Size‐resolved ice crystal particle concentrations and water vapor concentrations were measured to help identify the presence of cirrus clouds. About 72% of the in‐cloud samples showed new particle formation events with the average N4–9 of 3.0 × 103 cm−3, whereas about 56% of the out‐of‐cloud samples had events with the lower N4–9 of 1.3 × 103 cm−3. The periods during which high N4–9 appeared were often associated with times of increasing ice water content (IWC) and high relative humidity with respect to ice (RHI); however, the measured N4–9 was not quantitatively correlated to IWC. The magnitude and frequency of new particle formation events seen in cirrus clouds were also higher than those previously observed in the tropical/subtropical upper troposphere in the absence of clouds. These results suggest that cirrus clouds may provide favorable conditions for particle formation, such as low temperatures, high RHI, high OH production (due to high water vapor), cloud electricity, and atmospheric convection. At present, however, particle formation mechanisms in clouds are unidentified.
Crystal structure of 4-hydroxybutyryl-CoA dehydratase: Radical catalysis involving a [4Fe–4S] cluster and flavin
Authors: Martins Berta M. , Dobbek Holger , Çinkaya Irfan , Buckel Wolfgang , Messerschmidt Albrecht
Published: October 2004

Dehydratases catalyze the breakage of a carbon—oxygen bond leading to unsaturated products via the elimination of water. The 1.6-Å resolution crystal structure of 4-hydroxybutyryl-CoA dehydratase from the γ-aminobutyrate-fermenting
Clostridium aminobutyricum
represents a new class of dehydratases with an unprecedented active site architecture. A [4Fe–4S]
2+
cluster, coordinated by three cysteine and one histidine residues, is located 7 Å from the
Re
-side of a flavin adenine dinucleotide (FAD) moiety. The structure provides insight into the function of these ubiquitous prosthetic groups in the chemically nonfacile, radical-mediated dehydration of 4-hydroxybutyryl-CoA. The substrate can be bound between the [4Fe–4S]
2+
cluster and the FAD with both cofactors contributing to its radical activation and catalytic conversion. Our results raise interesting questions regarding the mechanism of acyl-CoA dehydrogenases, which are involved in fatty acid oxidation, and address the divergent evolution of the ancestral common gene.
Resolution of the novel immune-type receptor gene cluster in zebrafish
Authors: Yoder Jeffrey A. , Litman Ronda T. , Mueller M. Gail , Desai Salil , Dobrinski Kimberly P. , Montgomery Jennifer S. , Buzzeo Matthew P. , Ota Tatsuya , Amemiya Chris T. , Trede Nikolaus S. , Wei Sheng , Djeu Julie Y. , Humphray Sean , Jekosch Kerstin , Hernandez Prada Jose A. , Ostrov David A. , Litman Gary W.
Published: October 2004

The novel immune-type receptor (NITR) genes encode a unique multigene family of leukocyte regulatory receptors, which possess an extracellular Ig variable (V) domain and may function in innate immunity. Artificial chromosomes that encode zebrafish NITRs have been assembled into a contig spanning ≈350 kb. Resolution of the complete NITR gene cluster has led to the identification of eight previously undescribed families of NITRs and has revealed the presence of C-type lectins within the locus. A maximum haplotype of 36 NITR genes (138 gene sequences in total) can be grouped into 12 distinct families, including inhibitory and activating receptors. An extreme level of interindividual heterozygosity is reflected in allelic polymorphisms, haplotype variation, and family-specific isoform complexity. In addition, the exceptional diversity of NITR sequences among species suggests divergent evolution of this multigene family with a birth-and-death process of member genes. High-confidence modeling of Nitr V-domain structures reveals a significant shift in the spatial orientation of the Ig fold, in the region of highest interfamily variation, compared with Ig V domains. These studies resolve a complete immune gene cluster in zebrafish and indicate that the NITRs represent the most complex family of activating/inhibitory surface receptors thus far described.
A single active site residue directs oxygenation stereospecificity in lipoxygenases: Stereocontrol is linked to the position of oxygenation
Authors: Coffa Gianguido , Brash Alan R.
Published: October 2004

Lipoxygenases are a class of dioxygenases that form hydroperoxy fatty acids with distinct positional and stereo configurations. Several amino acid residues influencing regiospecificity have been identified, whereas the basis of stereocontrol is not understood. We have now identified a single residue in the lipoxygenase catalytic domain that is important for stereocontrol; it is conserved as an Ala in
S
lipoxygenases and a Gly in
R
lipoxygenases. Our results with mutation of the conserved Ala to Gly in two
S
lipoxygenases (mouse 8
S
-LOX and human 15-LOX-2) and the corresponding Gly–Ala substitution in two
R
lipoxygenases (human 12
R
-LOX and coral 8
R
-LOX) reveal that the basis for
R
or
S
stereo-control also involves a switch in the position of oxygenation on the substrate. After the initial hydrogen abstraction, antarafacial oxygenation at one end or the other of the activated pair of double bonds (pentadiene) gives, for example, 8
S
or 12
R
product. The Ala residue promotes oxygenation on the reactive pentadiene at the end deep in the substrate binding pocket and
S
stereochemistry of the product hydroperoxide, and a Gly residue promotes oxygenation at the proximal end of the reactive pentadiene resulting in
R
stereochemistry. A model of lipoxygenase reaction specificity is proposed in which product regiochemistry and stereochemistry are determined by fixed relationships between substrate orientation, hydrogen abstraction, and the Gly or Ala residue we have identified.
A biochemical oscillator explains several aspects ofMyxococcus xanthusbehavior during development
Authors: Igoshin Oleg A. , Goldbeter Albert , Kaiser Dale , Oster George
Published: October 2004

During development,Myxococcus xanthuscells produce a series of spatial patterns by coordinating their motion through a contact-dependent signal, the C-signal. C-signaling modulates the frequency at which cells reverse their gliding direction. It does this by interacting with the Frz system (a homolog of the Escherichia coli chemosensory system) via a cascade of covalent modifications. Here we show that introducing a negative feedback into this cascade results in oscillatory behavior of the signaling circuit. The model explains several aspects ofM. xanthusbehavior during development, including the nonrandom distribution of reversal times, and the differences in response of the reversal frequency to both moderate and high levels of C-signaling at different developmental stages. We also propose experiments to test the model.
Predominant K-ras Codon 12 G → A Transition in Chemically Induced Lung Neoplasms in B6C3F1 Mice
Authors: Ton Thai-Vu T. , Hong Hue-Hua L. , Anna Colleen H. , Dunnick June K. , Devereux Theodora R. , Sills Robert C. , Kim Yongbaek
Published: October 2004

Based on long-term toxicity and carcinogencity studies in B6C3F1 mice conducted by the National Toxicology Program, 2,2-Bis(bromomethyl)-1,3-propanediol (BMP) and tetranitromethane (TNM) have been identified as carcinogens. Following 2 yr of exposure to 312, 625, or 1,250 ppm BMP in feed, or exposure to 0.5 or 2 ppm TNM by inhalation, increased incidences of lung neoplasms were observed in B6C3F1 mice at all exposure concentrations compared to unexposed mice. The present study characterizes genetic alterations in the K- ras protooncogene in BMP- and TNM-induced lung neoplasms, respectively, and compares the findings to spontaneous lung neoplasms from corresponding control mice. The frequencies of the K- ras mutations were 57% (29/51) in BMP-induced lung neoplasms compared to 15% (3/20) in lung neoplasms from dosed feed control mice, and 54% (14/26) in TNM-induced lung neoplasms compared to 60% (3/5) in lung neoplasms from inhalation control mice. G → A transitions at the second base of the K- ras codon 12 (GGT → GAT) were the most frequent pattern of K- ras mutations identified in BMP-induced (20/29) and TNM-induced lung neoplasms (13/14), which differed from the mutational patterns identified in the lung neoplasms from unexposed control mice. These results indicate that mutations in the K- ras gene are involved in B6C3F1 lung carcinogenesis following BMP- and TNM-exposure, and the high frequency and specificity of the ras mutation profile in lung neoplasms (G → A transition) may be due to in vivo genotoxicity by the parent compounds or their metabolites.
Hexachlorobenzene-Induced Incisor Degeneration in Sprague—Dawley Rats
Authors: Long Philip H. , Herbert Ronald A. , Nyska Abraham
Published: October 2004

Hexachlorobenzene (HCB) was administered to female Sprague—Dawley rats in a 13-week toxicity study conducted for the National Toxicology Program (NTP). Groups of 10 rats were treated by gavage with 0.0, 0.03, 0.1, 0.3, 1.0, 3.0, 10, or 25 mg/kg HCB in corn oil 5 days/week for 13 weeks. Dose-dependent, region-specific, maxillary incisor degeneration was observed in animals given HCB at doses of 1.0 mg/kg/day and higher. Treatment with 1.0 mg/kg/day resulted in focal mesenchymal cell vacuolation and focal osteodentin formation within the pulp. Lesions were restricted to a short linear region subjacent to the odontoblast layer along the lateral aspect of the incisor at the level of the dentin-enamel interface. When observed in both incisors, lesions were bilaterally symmetric. Treatment with 3.0 mg/kg/day resulted in lateral and medial pulp lesions and focal odontoblast degeneration with dentin niche formation along the lateral incisor margin in some animals. Treatment with 10 mg/kg/day resulted in a higher incidence of lateral dentin niches and a low incidence of medial dentin niches. In animals treated with 25 mg/kg/day, a high incidence of bilaterally symmetric, lateral and medial, dentin niches were observed. The morphology and distribution of HCB-induced incisor lesions in rats are consistent with injury to a selective population of preodontoblasts.
Boron Supplementation Inhibits the Growth and Local Expression of IGF-1 in Human Prostate Adenocarcinoma (LNCaP) Tumors in Nude Mice
Authors: Gallardo-Williams Maria T. , Chapin Robert E. , King Paula E. , Moser Glenda J. , Goldsworthy Thomas L. , Morrison James P. , Maronpot Robert R.
Published: October 2004

Prostate-specific antigen (PSA) is a serine protease and one of the most abundant proteins secreted by the human prostate epithelium. PSA is used as a well-established marker of prostate cancer. The involvement of PSA in several early events leading to the development of malignant prostate tumors has made it a target for prevention and intervention. It is thought that PSA cleaves insulin-like growth factor binding protein-3 (IGFBP-3), providing increased local levels of IGF-1, leading to tumor growth. Separately, there are data that suggest an enzymatic regulatory role for dietary boron, which is a serine protease inhibitor. In this study we have addressed the use of boric acid as a PSA inhibitor in an animal study. We have previously reported that low concentrations (6 ug/mL) of boric acid can partially inhibit the proteolytic activity of purified PSA towards a synthetic fluorogenic substrate. Also, by Western blot we have followed the degradation of fibronectin by enzymatically active PSA and have found significant inhibition in the presence of boric acid. We proposed that dietary supplementation with boric acid would inhibit PSA and reduce the development and proliferation of prostate carcinomas in an animal model. We tested this hypothesis using nude mice implanted subcutaneously with LNCaP cells in Matrigel. Two groups (10 animals/group) were dosed with boric acid solutions (1.7, 9.0 mgB/kg/day) by gavage. Control group received only water. Tumor sizes were measured weekly for 8 weeks. Serum PSA and IGF-1 levels were determined at terminal sacrifice. The size of tumors was decreased in mice exposed to the low and high dose of boric acid by 38% and 25%, respectively. Serum PSA levels decreased by 88.6% and 86.4%, respectively, as compared to the control group. There were morphological differences between the tumors in control and boron-dosed animals, including a significantly lower incidence of mitotic figures in the boron-supplemented groups. Circulating IGF-1 levels were not different among groups, though expression of IGF-1 in the tumors was markedly reduced by boron treatment, which we have shown by immunohistochemistry. These data indicate that low-level dietary boron supplementation reduced tumor size and content of a tumor trophic factor, IGF-1.This promising model is being evaluated in further studies.
Zonal Distribution of Cell Proliferation in the Liver of Untreated B6C3F1 and C57BL Mice
Authors: Burkhardt Silke , Bahnemann Rainer , Failing Klaus , Reinacher Manfred
Published: October 2004

To determine the lobular distribution of hepatocellular proliferation, S-phase response was measured in untreated adult male B6C3F1 and C57BL mice at ages 11, 14, and 23 weeks. The percentage of cells in S-phase (labeling index, LI) was evaluated using immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU). The BrdU was delivered either by a single ip injection 2 hr prior to sacrifice or via an osmotic minipump implanted subcutaneously for 3 or 7 days. Mitotic and apoptotic indices were determined on H&E stained sections. Animals of both strains and all ages revealed highest LI in the intermediate compartment of the liver acinus (zone 2) irrespective of the length of BrdU application. Cell proliferation in this zone was at all time points significantly higher than elsewhere in the liver. The mitotic index confirmed the data obtained by the S-phase response study. Apoptosis was rarely observed. With regard to rodent data in chemical carcinogenesis and the way they should be evaluated, this study proved that the acinar distribution of proliferating cells in liver of mice is different from that in rats, since, according to the literature, rats reveal highest cell proliferative activity in the periportal zone.
Effects of Phonological and Orthographic Neighbourhood Density Interact in Visual Word Recognition
Authors: Grainger Jonathan , Muneaux Mathilde , Farioli Fernand , Ziegler Johannes C.
Published: October 2004

The present study investigated the role of phonological and orthographic neighbourhood density in visual word recognition. Three mechanisms were identified that predict distinct facilitatory or inhibitory effects of each variable. The lexical competition account predicts overall inhibitory effects of neighbourhood density. The global activation (familiarity) account predicts overall facilitatory effects of neighbourhood density. Finally, the cross-code consistency account predicts an interaction, with inhibition of phonological neighbours in sparse orthographic regions and facilitation of phonological neighbours in dense orthographic regions. In Experiment 1 (lexical decision), a cross-over interaction was indeed found, supporting the prediction of the cross-code consistency account. In Experiment 2, this cross-over interaction was exaggerated by adding pseudohomo-phone stimuli (e.g., brane) among the nonword targets. Finally, in Experiment 3 (progressive demasking), we tried to shift the balance between inhibitory and facilitatory mechanisms by using a perceptual identification task. As predicted, the inhibitory effects of phonological neighbourhood were amplified, whereas the facilitatory effects disappeared. We conclude that the level of compatibility across co-activated orthographic and phonological representations is a major causal factor underlying this pattern of effects.
Serial Position Memory in the Visual—Spatial Domain: Reconstructing Sequences of Unfamiliar Faces
Authors: Smyth Mary M. , Hay Dennis C. , Hitch Graham J. , Horton Neil J.
Published: October 2004

In two studies we presented pictures of unfamiliar faces one at a time, then presented the complete set at test and asked for serial reconstruction of the order of presentation. Serial position functions were similar to those found with verbal materials, with considerable primacy and one item recency, position errors that were mainly to the adjacent serial position, a visual similarity effect, and effects of articulatory suppression that did not interact with the serial position effect or with the similarity effect. Serial position effects were found when faces had been seen for as little as 300 ms and after a 6-s retention interval filled with articulatory suppression. Serial position effects found with unfamiliar faces are not based on verbal encoding strategies, and important elements of serial memory may be general across modalities.
Visual Memory for Objects in Natural Scenes: From Fixations to Object Files
Authors: Tatler Benjamin W. , Gilchrist Iain D. , Land Michael F.
Published: October 2004

Object descriptions are extracted and retained across saccades when observers view natural scenes. We investigated whether particular object properties are encoded and the stability of the resulting memories. We tested immediate recall of multiple types of information from real-world scenes and from computer-presented images of the same scenes. The relationship between fixations and properties of object memory was investigated. Position information was encoded and accumulated from multiple fixations. In contrast, identity and colour were encoded but did not require direct fixation and did not accumulate. In the current experiments, participants were unable to recall any information about shape or relative distances between objects. In addition, where information was encoded we found differential patterns of stability. Data from viewing real scenes and images were highly consistent, with stronger effects in the real-world conditions. Our findings imply that object files are not dependent upon the encoding of any particular object property and so are robust to dynamic visual environments.
Primary health care and hospital interactions: Effects for hospital length of stay
Authors: Kjekshus Lars Erik
Published: October 2004

Aims: Norwegian healthcare services are divided between primary and secondary care providers. A growing problem is that every third patient of 75 years of age or more experiences an extended stay in a somatic hospital while waiting to be sent to primary healthcare services. The interaction between these two levels of healthcare services is analysed to examine the effect on a patient's length of stay in hospital. Methods: Recent studies have asserted that research on length of stay in hospital should include influential factors such as system variation and system characteristics, in addition to standardizing for casemix. New organizational routines are identified in 50 Norwegian somatic hospitals. A multivariate linear regression is used in both a static and a dynamic model to explain variations in hospital length of stay and in additional length of stay (5% of stays are defined as outliers). Results: The study shows that newly specialized structures constructed to enhance the interaction between the two levels have had no effect. Length of stay is dependent on the capacity of the primary healthcare provider and on the share of elderly in the hospital catchment area, the type of patients, the procedure performed, and the characteristics of the hospital. Conclusion: Variation in length of stay between hospitals is primarily explained by the capacity of primary healthcare providers. However, some support is found in the dynamic model that introduces the proposition that a hospital-owned hotel would decrease the length of stay of patients in hospital.
Who are the ``quitters''? a cross-sectional study of circumstances associated with women giving up smoking
Authors: Janzon Ellis , Engström Gunnar , Lindström Martin , Berglund Göran , Hedblad BO , Janzon Lars
Published: October 2004

Background: Smoking is an important preventable risk factor for cardiovascular disease, cancer, and many other diseases. Even though tobacco consumption is declining in Sweden, it is not declining in all groups. This study explored socioeconomic and psychosocial circumstances hindering or facilitating smoking cessation in three birth cohorts of women from the general population. Methods: Between 1991 and 1996 a comprehensive questionnaire was administered to 17,319 women, 45—73 years old, from the Malmö Diet and Cancer cohort. Smoking habits were compared in relation to socioeconomic and psychosocial circumstances in three birth cohorts. Results: Of these women, 44% were never smokers, 28% were ex-smokers, and 28% were smokers (regular or occasional). When compared with smokers, ex-smokers were more often married, had a higher socioeconomic position, a longer education, more smoke-free surroundings, better emotional support, higher BMI, and better self-perceived health. Ex-smokers reported less work-related stress and less shift work. A history of cardiovascular disease was not associated with smoking cessation. The socioeconomic differences between current and former smokers were higher for young women as compared with older birth cohorts. Conclusions: Continuing smokers and quitters differ with regard to socioeconomic and psychosocial circumstances and factors related to working life and environmental tobacco exposure. By determining who the quitters are through continued follow-up, useful insights can be gained to develop strategies to achieve successful cessation of smoking.
The Efficiency of Protein Compartmentalization into the Secretory Pathway
Authors: Levine Corinna G. , Mitra Devarati , Sharma Ajay , Smith Carolyn L. , Hegde Ramanujan S.
Published: October 2004

Numerous proteins targeted for the secretory pathway are increasingly implicated in functional or pathological roles at alternative cellular destinations. The parameters that allow secretory or membrane proteins to reside in intracellular locales outside the secretory pathway remain largely unexplored. In this study, we have used an extremely sensitive and quantitative assay to measure the in vivo efficiency of signal sequence-mediated protein segregation into the secretory pathway. Our findings reveal that segregation efficiency varies tremendously among signals, ranging from >95 to <60%. The nonsegregated fraction is generated by a combination of mechanisms that includes inefficient signal-mediated translocation into the endoplasmic reticulum and leaky ribosomal scanning. The segregation efficiency of some, but not other signal sequences, could be influenced in cis by residues in the mature domain or in trans by yet unidentified cellular factors. These findings imply that protein compartmentalization can be modulated in a substrate-specific manner to generate biologically significant quantities of cytosolically available secretory and membrane proteins.
Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol
Authors: Acconcia Filippo , Ascenzi Paolo , Bocedi Alessio , Spisni Enzo , Tomasi Vittorio , Trentalance Anna , Visca Paolo , Marino Maria
Published: October 2004

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.
Mammalian Protein SCP1 Forms Synaptonemal Complex-like Structures in the Absence of Meiotic Chromosomes
Authors: Öllinger Rupert , Alsheimer Manfred , Benavente Ricardo
Published: October 2004

Synaptonemal complexes (SCs) are evolutionary conserved, meiosis-specific structures that play a central role in synapsis of homologous chromosomes, chiasmata distribution, and chromosome segregation. However, it is still for the most part unclear how SCs do assemble during meiotic prophase. Major components of mammalian SCs are the meiosis-specific proteins SCP1, 2, and 3. To investigate the role of SCP1 in SC assembly, we expressed SCP1 in a heterologous system, i.e., in COS-7 cells that normally do not express SC proteins. Notably, under these experimental conditions SCP1 is able to form structures that closely resemble SCs (i.e., polycomplexes). Moreover, we show that mutations that modify the length of the central α-helical domain of SCP1 influence the width of polycomplexes. Finally, we demonstrate that deletions of the nonhelical N- or C-termini both affect polycomplex assembly, although in a different manner. We conclude that SCP1 is a primary determinant of SC assembly that plays a key role in synapsis of homologous chromosomes.
Proteomic Analysis of theArabidopsisNucleolus Suggests Novel Nucleolar Functions
Authors: Pendle Alison F. , Clark Gillian P. , Boon Reinier , Lewandowska Dominika , Lam Yun Wah , Andersen Jens , Mann Matthias , Lamond Angus I. , Brown John W. S. , Shaw Peter J.
Published: October 2004

The eukaryotic nucleolus is involved in ribosome biogenesis and a wide range of other RNA metabolism and cellular functions. An important step in the functional analysis of the nucleolus is to determine the complement of proteins of this nuclear compartment. Here, we describe the first proteomic analysis of plant (Arabidopsis thaliana) nucleoli, in which we have identified 217 proteins. This allows a direct comparison of the proteomes of an important nuclear structure between two widely divergent species: human and Arabidopsis. The comparison identified many common proteins, plant-specific proteins, proteins of unknown function found in both proteomes, and proteins that were nucleolar in plants but nonnucleolar in human. Seventy-two proteins were expressed as GFP fusions and 87% showed nucleolar or nucleolar-associated localization. In a striking and unexpected finding, we have identified six components of the postsplicing exon-junction complex (EJC) involved in mRNA export and nonsense-mediated decay (NMD)/mRNA surveillance. This association was confirmed by GFP-fusion protein localization. These results raise the possibility that in plants, nucleoli may have additional functions in mRNA export or surveillance.
Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies
Authors: Brien Sarah , Lewith George , Walker Ann , Hicks Stephen M. , Middleton Dick
Published: October 2004

Bromelain, an extract from the pineapple plant, has been demonstrated to show anti‐inflammatory and analgesic properties and may provide a safer alternative or adjunctive treatment for osteoarthritis. All previous trials, which have been uncontrolled or comparative studies, indicate its potential use for the treatment of osteoarthritis. This paper reviews the mechanism of its putative therapeutic actions, those clinical trials that have assessed its use in osteoarthritis to date, as well as considering the safety implications of this supplement for osteoarthritis and reviewing the evidence to date regarding the dosage for treating this condition. The data available at present indicate the need for trials to establish the efficacy and optimum dosage for bromelain and the need for adequate prospective adverse event monitoring in such chronic conditions as osteoarthritis.