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The solvent mediated force between the hard solutes mimicking liophobic colloids in Baxter’s adhesive solvent is studied on the basis of the solution to the Percus–Yevick/Ornstein–Zernike equation for spatial correlations in an infinitely dilute solution. The contact value of the solute–solute potential of mean force remains the same as observed previously in hard sphere fluid but its range increases in the presence of the attractive interaction among the molecules of the solvent. At the critical conditions of the model fluid, the solvation force between the macroparticles tends to vanish in parallel with the increasing compressibility of the fluid. The size dependence of the intercolloidal interaction is similar but slightly more pronounced than found in fluids with pure hard core interaction. [ABSTRACT FROM AUTHOR]

Background: Hypoplastic left heart syndrome (HLHS) covers a spectrum of rare congenital anomalies characterised by a non-apex forming left ventricle and stenosis/atresia of the mitral and aortic valves. Despite many studies, the causes of HLHS remain unclear and there are conflicting views regarding the role of flow, valvar or myocardial abnormalities in its pathogenesis, all of which were proposed prior to the description of the second heart field. Our aim was to re-evaluate the patterns of malformation in HLHS in relation to recognised cardiac progenitor populations, with a view to providing aetiologically useful sub-groupings for genomic studies.Results: We examined 78 hearts previously classified as HLHS, with subtypes based on valve patency, and re-categorised them based on their objective ventricular phenotype. Three distinct subgroups could be identified: slit-like left ventricle (24%); miniaturised left ventricle (6%); and thickened left ventricle with endocardial fibroelastosis (EFE; 70%). Slit-like ventricles were always found in combination with aortic atresia and mitral atresia. Miniaturised left ventricles all had normally formed, though smaller aortic and mitral valves. The remaining group were found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis. The degree of myocardial thickening was not correlated to the degree of valvar stenosis. Lineage tracing in mice to investigate the progenitor populations that form the parts of the heart disrupted by HLHS showed that whereas Nkx2-5-Cre labelled myocardial and endothelial cells within the left and right ventricles, Mef2c-AHF-Cre, which labels second heart field-derived cells only, was largely restricted to the endocardium and myocardium of the right ventricle. However, like Nkx2-5-Cre, Mef2c-AHF-Cre lineage cells made a significant contribution to the aortic and mitral valves. In contrast, Wnt1-Cre made a major contribution only to the aortic valve. This suggests that discrete cardiac progenitors might be responsible for the patterns of defects observed in the distinct ventricular sub-groups.Conclusions: Only the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. It appears that slit-like and miniature ventricles also form discrete sub-groups. Thus, reclassification of HLHS into subgroups based on ventricular phenotype, might be useful in genetic and developmental studies in investigating the aetiology of this severe malformation syndrome. [ABSTRACT FROM AUTHOR]

The roof-to-wall connection in a house is designed to transfer the uplift and lateral loads during strong winds by providing a continuous load path from the roof to the foundation. The uplift capacity and failure mode of the connection depends on the number and type of fasteners (nails), timber species, type of framing anchor, and constructions defects. This paper presents experimental results that were used to assess the uplift capacity variation of typical roof-to-wall connections. Based on tests with two types of connections (triple grip and truss grip) assembled with two types of timber (radiata pine and spruce pine), nails (hand and gun), and framing anchors (triple grip and universal triple grip), the results show that the variation in timber species, nail, and triple grip type changes the strength and the failure modes of the connection. The strength of the connection was reduced by about 24% when the timber species was changed from radiata pine to spruce pine and the hand nail to gun nail on the triple grip connection. This study also showed that construction defects in roof-to-wall connections influence the design uplift capacity. If there are two missing nails in the hand-nailed triple grip connection (i.e., one nail on the truss and another one on the top plate) the design uplift capacity reduces by about 40% of the ideal hand-nailed triple grip connection. This study identified the critical nails and their locations required to mitigate failure of the roof-to-wall triple grip connection subject to wind loading. [ABSTRACT FROM AUTHOR]

Design pressures given in wind loading standards are based on wind tunnel studies conducted during the 1970s to 90s on rectangular hip and gable roofs. However, most contemporary houses have complex hip-roof geometries with a range of plan footprints. Wind tunnel model studies were carried out on representative one- and two-storey houses to determine cladding design and truss hold-down loads. These loads were compared to design loads determined from wind loading standards AS/NZS 1170.2 and AS 4055. AS 4055 gave conservative design loads in most situations, and AS/NZS 1170.2 underestimated the loads near the windward edges and ridge on the roof. AS/NZS 1170.2 does give satisfactory design loads for wall cladding and truss hold down. [ABSTRACT FROM PUBLISHER]

Background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples.Methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold>3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample.Results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC).Conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression. [ABSTRACT FROM AUTHOR]

Background:Isoforms of the PDE4 family of cAMP-specific phosphodiesterases (PDEs) are expressed in a cell type-dependent manner and contribute to underpinning the paradigm of intracellular cAMP signal compartmentalisation. Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression and uncover a role in controlling prostate cancer cell proliferation.Methods:PDE4 transcripts from 19 prostate cancer cell lines and xenografts were quantified by qPCR. PDE4D7 expression was further investigated because of its significant downregulation between androgen-sensitive (AS) and androgen-insensitive (AI) samples. Western blot analysis, PDE activity assay, immunofluorescent staining and cAMP responsive FRET assays were used to investigate the sub-plasma membrane localisation of a population of PDE4D7 in VCaP (AS) and PC3 (AI) cell lines. Disruption of this localisation pattern using dominant-negative protein expression and siRNA knockdown showed that PDE4D7 acts in opposition to proliferative signalling as assessed by electrical impedance-based proliferation assays.Results:Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression. PDE4D7 is highly expressed in AS cells and starkly downregulated in AI samples. The significance of this downregulation is underscored by our finding that PDE4D7 contributes a major fraction of cAMP degrading PDE activity tethered at the plasma membrane and that displacement of PDE4D7 from this compartment leads to an increase in the proliferation of prostate cancer cells. PDE4D7 mRNA expression is not, however, directly regulated by the androgen receptor signalling axis despite an overlapping genomic structure with the androgen responsive gene PART1. PDE4D7, which locates to the plasma membrane, acts to supress aberrant non-steroidal growth signals within the prostate or AS metastasis.Conclusions:PDE4D7 expression is significantly downregulated between AS and AI cell phenotypes. This change in expression potentially provides a novel androgen-independent biomarker and manipulation of its activity or its expression may provide therapeutic possibilities and insights into contributory aspects of the complex molecular pathology of prostate cancer. [ABSTRACT FROM AUTHOR]

Our Fortran codes for hard sphere fluids and their mixtures for the correlation functions that arise from the Percus-Yevick theory and the Verlet-Weis semi-empirical correction have proven useful during a period of nearly four decades and continue to be useful. In order to make these codes even more widely available, a brief summary is presented here and listings of these codes are given in the electronically accessible Supplementary Material to this paper. [ABSTRACT FROM AUTHOR]

This paper assesses the damage to high-set rectangular-plan houses with low-pitch gable roofs (built in the 1960 and 70s in the northern parts of Australia) to wind speeds experienced in tropical cyclones. The study estimates the likely failure mode and percentage of failure for a representative proportion of houses with increasing wind speed. Structural reliability concepts are used to determine the levels of damage. The wind load and the component connection strengths are treated as random variables with log-normal distributions. These variables are derived from experiments, structural analysis, damage investigations and experience. This study also incorporates progressive failures and considers the interdependency between the structural components in the house, when estimating the types and percentages of the Overall failures in the population of these houses. The progressively increasing percentage of houses being subjected to high internal pressures resulting from damage to the envelope is considered. Results from this study also compare favourably with levels of damage and related modes of failure for high-set houses observed in post-cyclone damage surveys. [ABSTRACT FROM AUTHOR]

Drug abuse is the primary reason women enter prison and is the primary health problem of women in prison. There has been little research conducted specifically with this population; information must be drawn from studies with nonincarcerated addicted women and incarcerated addicted men. The purpose of this paper is to review what is known about the treatment and aftercare needs of this group (including relapse and recidivism prevention) and to propose an agenda for future research. [ABSTRACT FROM AUTHOR]

The immunosuppressive compounds FK-506, cyclosporin A (CsA) and rapamycin inhibit both the human and mouse mixed lymphocyte reactions (MLR) with IC50s of 2-5 × 10-10 M for FK-506 and rapamycin and 10-8 M for CsA. FK-506 and CsA were also potent inhibitors of A23187/PMA- stimulated IL-2 production by Jurkat and HuT-78 cells but had no effect on the response of mouse CTLL cells to IL-2. IC50 values for inhibition of IL-2 production closely matched those for inhibition of the M LR and both drugs were active only during the first 4-6 hr following stimulation. In contrast, rapamycin was a poor inhibitor of 1L-2 production, although it inhibited cellular responses to IL-2. The IC50 values for these two activities indicated that neither alone accounted for rapamycin inhibition of the MLR. FK-506 and CsA affected IL-2 gene transcription in Jurkat cells by the same mechanism. Both inhibited the appearance of the transcription factor, NFAT, whereas rapamycin did not. The appearance of another transcription factor, NFKβ, was unaffected by all three drugs. The effects of FK-506 and CsA on IL-2 gene expression, therefore, are similar even though the two drugs act through distinct cytosolic receptors. [ABSTRACT FROM AUTHOR]

The mini-circle is a transposable element which is present in Streptomyces coelicolor A3(2) in both free circular and chromosomally integrated linear forms. The nucleotide sequences of the mini-circle and its preferred site of integration in the Streptomyces lividans TK64 chromosome were determined. Three putative open reading frames were identified in the mini-circle sequence. The mini-circle does not appear to cause a target site duplication on transposition and does not have perfect terminal inverted repeats. The observed site-specificity of the mini-circle is not mediated by extensive homology between the element and the chromosomal integration site. Transposition of the mini-circle into the S. lividans chromosome was demonstrated and found to be some two orders of magnitude less efficient than integration of the circular form of the element, suggesting that the circular form of the mini-circle might be a normal intermediate in the transposition process. [ABSTRACT FROM AUTHOR]

The expression of the placental proteins human chorionic gonadotrophin alpha (HCG alpha), beta (HCG beta) and human placental lactogen (HPL) was examined in trophoblast from human normal pregnancy and early embryonic failure (EEF) using Northern blot analysis. Trophoblast from EEF expressed significantly depressed levels of HCG alpha (P < 0.05) and HCG beta (P < 0.01) when compared to normal pregnancy. Levels of expression of HPL in EEF were not significantly different to those from normal pregnancy. The gestational ages of the two groups were not significantly different. Immunocytochemistry on paraffin-fixed tissue sections supported these data and showed that mRNA levels reflected protein production of HCG within the tissue. It appears from these data that the depressed level of HCG found in the serum of women with early pregnancy failure is not solely a consequence of diminished placentation in these pregnancies, or placental necrosis, but that the genes of the alpha and beta HCG subunits are down-regulated. This study further suggests that there are two subsets of women with early pregnancy failure; those with apparently normal levels of placental proteins, and those with severely depressed levels. It would seem likely that these two groups have different aetiologies. [ABSTRACT FROM AUTHOR]

Purpose: Malformations affecting the outflow of the heart are a major cause of morbidity and mortality in childhood. While many of these malformations occur sporadically, studies of families with congenital heart defects, alongside animal studies, have revealed that phenotypically discrete heart malformations can have diverse causes, resulting from disruption of a number of different genes, embryonic lineages or developmental processes. Clarifying the fundamental processes that underpin outflow development is essential to understand this complexity. Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. Our objective was to establish which of the several cell lineages that form the developing heart require Vangl2-regulated PCP signalling and why disruption leads to outflow tract defects.Methods and Results: Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Thus, in the absence of Vangl2 in the SHF the mice develop double outlet right ventricle and ventricular septal defects. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-associated Vangl2 marks the proximal extent of this transition zone and, moreover, in the absence of Vangl2, the SHF-derived cells are abnormally polarised cells and do not acquire an epithelial phenotype. As a consequence they prematurely down-regulate the SHF-progenitor marker Isl1 and differentiate to cardiomyocytes. This leads to a shortened outflow tract.Conclusion: Vangl2-regulated polarisation and consequent epithelialisation of the distal outflow tract is essential to lengthen the tubular outflow vessel. This leads to the double outlet right ventricle and ventricular septal defects. [ABSTRACT FROM AUTHOR]

The article presents a correction to the article "Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates," which was published in the previous issues of the journal "Nature Genetics."

This paper describes architectures and significant implementation features of two systems in the IBM POWER8i processor-based family of servers. Specifically, the scale-out 2-socket rack server and the enterprise scale-up 16-socket rack server are detailed. The description of these systems highlights the increase in memory bandwidth from previous POWERA systems, the enablement of coherent accelerators, the highly-extensible I/O subsystem, and the high-performance directly attached storage subsystem. In addition, reliability, availability, and serviceability features are described. These systems deliver significant increases in core count, memory, and input/output bandwidth over previous POWER systemsVwith reliability and availability enhancements commensurate with the performance improvements. [ABSTRACT FROM AUTHOR]

The extinct p-process nuclide 146Sm serves as an astrophysical and geochemical chronometer through measurements of isotopic anomalies of its α-decay daughter 142Nd. Based on analyses of 146Sm/147Sm α-activity and atom ratios, we determined the half-life of 146Sm to be 68 ± 7 (1δ) million years, which is shorter than the currently used value of 103 ± 5 million years. This half-life value implies a higher initial 146Sm abundance in the early solar system, (146Sm/144Sm)o = 0.0094 ± 0.0005 (2δ), than previously estimated. Terrestrial, lunar, and martian planetary silicate mantle differentiation events dated with 146Sm-142Nd converge to a shorter time span and in general to earlier times, due to the combined effect of the new 146Sm half-life and (146Sm/144Sm)o values. [ABSTRACT FROM AUTHOR]

The extinct p-process nuclide (146)Sm serves as an astrophysical and geochemical chronometer through measurements of isotopic anomalies of its α-decay daughter (142)Nd. Based on analyses of (146)Sm/(147)Sm α-activity and atom ratios, we determined the half-life of (146)Sm to be 68 ± 7 (1σ) million years, which is shorter than the currently used value of 103 ± 5 million years. This half-life value implies a higher initial (146)Sm abundance in the early solar system, ((146)Sm/(144)Sm)(0) = 0.0094 ± 0.0005 (2σ), than previously estimated. Terrestrial, lunar, and martian planetary silicate mantle differentiation events dated with (146)Sm-(142)Nd converge to a shorter time span and in general to earlier times, due to the combined effect of the new (146)Sm half-life and ((146)Sm/(144)Sm)(0) values.

The 44Ti(t1/2=59 yr) nuclide, an important signature of supernova nucleosynthesis, has recently been observed as live radioactivity by gamma-ray astronomy from the Cas A remnant. We investigate in the laboratory the major 44Ti production reaction 40Ca(alpha, gamma)44Ti (Ec.m. approximately 0.6-1.2 MeV/u by direct off-line counting of 44Ti nuclei. The yield, significantly higher than inferred from previous experiments, is analyzed in terms of a statistical model using microscopic nuclear inputs. The associated stellar rate has important astrophysical consequences, increasing the calculated supernova 44Ti yield by a factor approximately 2 over previous estimates and bringing it closer to Cas A observations.

The 62Ni(n,gamma)63Ni(t(1/2)=100+/-2 yr) reaction plays an important role in the control of the flow path of the slow neutron-capture (s) nucleosynthesis process. We have measured for the first time the total cross section of this reaction for a quasi-Maxwellian (kT=25 keV) neutron flux. The measurement was performed by fast-neutron activation, combined with accelerator mass spectrometry to detect directly the 63Ni product nuclei. The experimental value of 28.4+/-2.8 mb, fairly consistent with a recent calculation, affects the calculated net yield of 62Ni itself and the whole distribution of nuclei with 62

We have studied the 2H(8Li,p)9Li reaction to obtain information on the spins, parities, and single-neutron spectroscopic factors for states in 9Li, using a radioactive 8Li beam. The deduced properties of the lowest three states are compared to the predictions of a number of calculations for the structure of 9Li. The results of ab initio quantum Monte Carlo calculations are in good agreement with the observed properties.

To develop a suitable single photon emission computed tomography (SPECT) radioligand for neuronal nicotinic acetylcholine receptors (nAChRs) that displays faster in vivo kinetics than 5-[123I]iodo-A-85380, we synthesised the radioiodinated analogue of A-84543. 5-[123I]Iodo-A-84543 was prepared by electrophilic iododestannylation in a modest yield of 23%. In the baboon brain, 5-[123I]iodo-A-85380 displayed a profile consistent with the known distribution of nAChRs, however, 5-[123I]iodo-A-84543 displayed a homogenous uptake with no preferential localisation in regions known to contain nAChRs. To examine the effect of halogen substitution on the 3-pyridyl ether, A-84543, the 5-chloro, 5-bromo and 5-iodo analogues were synthesised and evaluated with respect to nAChR binding. In vitro binding data revealed that halogen substitution at the 5-position of A-84543 was not well tolerated with an increase in halogen size resulting in lower binding towards nAChRs. The 5-chloro analogue 4 displayed highest affinity, Ki =1.3 nM, compared to the 5-bromo and 5-iodo compounds, 5 Ki =3.3 nM and 3 Ki =40.8 nM, respectively. Taken together, these results clearly indicate that 5-[123I]iodo-A-84543 is not suitable for the study of nAChRs in vivo using SPECT.

The excitation function for fusion evaporation in the (60)Ni+ (89)Y system was measured over a range in cross section covering 6 orders of magnitude. The cross section exhibits an abrupt decrease at extreme sub-barrier energies. This behavior, which is also present in a few other systems found in the literature, cannot be reproduced with present models, including those based on a coupled-channels approach. Possible causes are discussed, including a dependence on the intrinsic structure of the participants.

The chirality that is inherent in the enzyme systems of living organisms results in an abundance of enantiopure organic molecules in the living world. In addition to the optical properties first noticed by Pasteur, stereospecific interactions at recognition sites result in differences in both biological and toxicological effects. This fact underlies the continuing growth in chiral chemistry, rooted as it is in fundamental biochemistry. The pharmaceutical industry has undergone a strategic shift and embraced the wide spectrum of asymmetrical synthetic methods now available. The use of these processes in developmental synthesis and large-scale manufacturing has provided new challenges in drug discovery, motivated by a desire to improve industrial efficacy and decrease the time from the conception of a new drug to the market. The economic impact of the industrial production of chiral drugs is now huge--more than 50% of the 500 top-selling drugs were single-enantiomers in 1997. Sales have continued to increase by more than 20% for the past 6 yr and worldwide annual sales of enantiomeric drugs exceeded US$100 billion for the first time in the year 2000, chiral drugs representing close to one-third of all sales worldwide. While some 'chiral switches' may be of less apparent benefit, or indeed detrimental in some cases, encouragement by the regulatory agencies and the ability to extend the life cycle of a drug coming off patent promotes the trend. However, it may turn out to be the ability to provide chiral templates, and thereby attack the key targets of selectivity and specificity, that will lead to the greatest benefits. Research into new chemical entities that can interact specifically with enzyme families may potentially lead to new therapies for complex disease processes. As Richards has stated, the approach is designed to create a made to measure product, rather than one off the peg.

The protein EP300 and its paralog CREBBP (CREB-binding protein) are ubiquitously expressed transcriptional co-activators and histone acetyl transferases. The gene EP300 is essential for normal cardiac and neural development, whereas CREBBP is essential for neurulation, hematopoietic differentiation, angiogenesis and skeletal and cardiac development. Mutations in CREBBP cause Rubinstein-Taybi syndrome, which is characterized by mental retardation, skeletal abnormalities and congenital cardiac defects. The CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) binds EP300 and CREBBP with high affinity and regulates gene transcription. Here we show that Cited2-/- embryos die with cardiac malformations, adrenal agenesis, abnormal cranial ganglia and exencephaly. The cardiac defects include atrial and ventricular septal defects, overriding aorta, double-outlet right ventricle, persistent truncus arteriosus and right-sided aortic arches. We find increased apoptosis in the midbrain region and a marked reduction in ErbB3-expressing neural crest cells in mid-embryogenesis. We show that CITED2 interacts with and co-activates all isoforms of transcription factor AP-2 (TFAP2). Transactivation by TFAP2 isoforms is defective in Cited2-/- embryonic fibroblasts and is rescued by ectopically expressed CITED2. As certain Tfap2 isoforms are essential in neural crest, neural tube and cardiac development, we propose that abnormal embryogenesis in mice lacking Cited2 results, at least in part, from its role as a Tfap2 co-activator.

Loop-tail (Lp) is a naturally occurring mouse mutant that develops severe neural tube defects. In this study, we describe complex cardiovascular defects in Lp homozygotes, which include double-outlet right ventricle, with obligatory perimembranous ventricular septal defects, and double-sided aortic arch, with associated abnormalities in the aortic arch arteries. Outflow tract and aortic arch defects are often related to abnormalities in the cardiac neural crest, but using molecular and anatomic markers, we show that neural crest migration is normal in Lp/Lp embryos. On the other hand, the heart fails to loop normally in Lp/Lp embryos, in association with incomplete axial rotation and reduced cervical flexion. As a consequence, the ventricular loop is shifted posteromedially relative to its position in wild-type embryos. This suggests that the observed cardiac alignment defects in the Lp mutant may be secondary to failure of neural tube closure and incomplete axial rotation. Double-sided aortic arch is a rare finding among mouse models. In humans, it is usually an isolated malformation, only rarely occurring in combination with other cardiac defects. We suggest that the double-sided arch arises as a primary defect in the Lp mutant, unrelated to the alignment defects, perhaps reflecting a role for the (as-yet-unknown) Lp gene in maintenance/regression of the aortic arch system.

The aim of this study was to examine the frequency with which soil samples require to be taken in order to determine significant temporal changes in soil properties. The examination was carried out using data from Glensaugh Research Station in north-east Scotland where podzolic soils were sampled in 1956, 1977 and 1997, and by re-analysis of archived material. Significant differences in chemistry due to storage were detected, particularly decreases in pH of air-dried organic soils. In these cases original data were used for statistical analysis to establish changes between 1956 and 1997. Temporal changes were found for exchangeable Ca and Mg which generally decreased with time throughout the soil profile, whereas exchangeable H increased. Derived data, such as percent base saturation, declined dramatically due to decreases in exchangeable base cations. Similar podzolic soils were sampled at an adjacent Environmental Change Network (ECN) site in 1993. Application of statistical techniques to the ECN soil chemistry data allowed an estimation of the detectable change between any two years. These data along with the rates of temporal change from 1956 to 1997 allowed the calculation of the number of years required for measurable changes to be achieved. These changes and sampling intervals vary among different horizons and chemistries. Although they are site-specific, they do confirm that the current ECN protocols of a 5-year and 20-year sampling would be appropriate in order to detect changes in soil properties over time at this site.

T-box transcription factors contain a novel type of DNA-binding domain, the T-box domain, and are encoded by an ancient gene family. Four T-box genes, omb, Trg, org-1, and H15, have been identified in Drosophila, whereas in mammals the T-box gene family has expanded, and 12 human T-box genes have been isolated. We have identified a new human T-box gene, TBX20, and its mouse homologue Tbx20, which are more closely related to the Drosophila H15 gene than to any known vertebrate gene. H15 expression in leg imaginal discs correlates with commitment to a ventral fate, implicating this gene in early patterning events. We find that TBX20 is expressed in the fetal heart, eye, and limb, and during embryogenesis in the mouse, Tbx20 is expressed in the developing heart, eye, ventral neural tube, and limbs, indicating a possible role in regulating development of these tissues. The TBX20 gene maps to chromosome 7p14-p15. An association between TBX20 and loci for retinitis pigmentosa, RP9, and blepharophimosis syndrome, BPES, have been excluded., (Copyright 2000 Academic Press.)

RhoB mRNA expression was examined in the developing mouse embryo between E8.5 and E11.5. Specific expression was found in migrating neural crest (NC) cells, from the first stages of their migration at E9.5, throughout the migration period. Expression is maintained in NC derivatives for at least one embryonic day after they reach their final destinations, but is then down-regulated. RhoB is also expressed in non NC-derived neural tissues, including motor neurones and the floor plate of the neural tube. RhoB mRNA expression is also found in the developing endocardial cushions of the atrioventricular and outflow regions of the developing heart.

Unlabelled: We studied the effect of dextromethorphan, an N-methyl-D-aspartate antagonist, on analgesic consumption and pain scoring after abdominal hysterectomy. In this double-blinded study, 50 patients were randomized into two groups. Group DM was given oral dextromethorphan 40 mg with their premedication, then 40 mg three times per day for the next 2 days. Group P received placebo at identical times. Postoperative analgesic requirements were assessed using a patient-controlled analgesia system and subsequent oral analgesic intake using a set protocol. Pain was assessed at rest and on movement using a visual analog scale 4, 24, 48, and 72 h after the operation. Median pain scores at rest were significantly lower at 48 and 72 h and also for the sum of all resting pain scores. Mean morphine consumption was less in Group DM (1.1 vs 1.5 mg/h; P = 0.054). Usage of oral diclofenac, given every 8 h as needed, did not differ between groups, but consumption of codydramol (paracetamol 500 mg and dihydrocodeine 10 mg) was significantly less in Group DM. We conclude that the use of oral dextromethorphan has an analgesia-sparing effect and some beneficial effects on pain scoring at rest after abdominal hysterectomy., Implications: Patients given dextromethorphan before and after surgery had a significant reduction in some pain scores at rest, but not on movement. There was a trend to lower morphine requirements in the first 24 h. Over the next 48 h, oral analgesic usage was significantly reduced.

The splotch (Pax3) mouse mutant serves as a model for developmental defects of several types, including defective migration of dermomyotomal cells to form the limb musculature. Here, we describe abnormalities of the ribs, neural arches, and acromion in Sp2H homozygous embryos, indicating a widespread dependence of lateral somite development on Pax3 function. Moreover, the intercostal and body wall muscles, derivatives of the ventrolateral myotome, are also abnormal in Sp2H homozygotes. Pax3 is expressed in the dermomyotome, but not in either the sclerotome or the myotome, raising the possibility that Pax3-dependent inductive influences from the dermomyotome are necessary for early specification of lateral sclerotome and myotome. Support for this idea comes from analysis of gene expression markers of lateral sclerotome (tenascin-C and scleraxis) and myotome (myogenin, MyoD, and Myf5). All exhibit ventrally truncated domains of expression in Sp2H homozygotes, potentially accounting for the rib and intercostal muscle truncations. In contrast, the medial sclerotomal marker Pax1 is expressed normally in mutant embryos, arguing that Pax3 is not required for development of the medial sclerotome. Most of the somitic markers show ectopic expression in anteroposterior and mediolateral dimensions, suggesting a loss of definition of somite boundaries in splotch and explaining the rib and muscle fusions. An exception is Myf5, which is not ectopically expressed in Sp2H homozygotes, consistent with the previous suggestion that Pax3 and Myf5 function in different pathways of skeletal myogenesis. PDGFalpha and its receptor are candidates for mediating signalling between myotome and sclerotome. We find that both genes are misexpressed in Sp2H embryos, suggesting that PDGFalpha/PDGFRalpha may function downstream of Pax3, accounting for the close similarities between the splotch and Patch mutant phenotypes. Our findings point to additional regulatory functions for the Pax3 transcription factor, apart from those already demonstrated for development of the neural tube, neural crest, and dermomyotome., (Copyright 1999 Academic Press.)

Degenerate PCR was used to amplify DNAs encoding members of the P2Y receptor family from rat brain RNA. A full-length sequence obtained for one novel clone (R5) contained an intronless open reading frame that encoded a polypeptide of 361 amino acids, sharing 84% sequence identity with the human P2Y4 receptor. When R5 was stably expressed in Jurkat cells, calcium fluxes resulting from stimulation of the receptor showed that UDP, ADP, 2-methylthio-ATP, and diadenosine tetraphosphate were inactive, whereas UTP and ATP were both full agonists with similar potency. At the human receptor, ATP has significantly lower potency than UTP. The R5 transcript was not detected in brain by northern hybridization. Therefore, its tissue distribution was assessed by PCR, and the mRNA was found to be widely distributed at a low abundance, being present in brain, spinal cord, and a variety of peripheral organs. Localization of the receptor transcript in adult rat brain sections by in situ hybridization indicated that it is expressed at highest levels in the pineal gland and ventricular system. It is presumed that R5 is a species orthologue of the human P2Y4 receptor but with this significant difference in agonist pharmacology.

The versican (PG-M) gene encodes a chondroitin sulfate proteoglycan that is nonpermissive for cell migration and appears in association with slow cell proliferation and cytodifferentiation. Using the techniques of in situ hybridization and immunocytochemistry on sectioned mouse embryos, we found that the mRNA and protein for versican show similar distributions and are expressed in a dynamic pattern during development of the heart. Versican exhibits generalized expression in the tubular heart but becomes rapidly downregulated in the atrium and exhibits higher transcript levels on the right side of the ventricular chamber than the left, before the onset of ventricular septation. Versican is expressed strongly in the trabeculated ventricular myocardium, whereas the compact proliferative zone has lower transcript abundance. It is expressed in the outer layers and on the crest of the ventricular septum and is prominent on the mesenchymal cap of the primary atrial septum. Versican is particularly strongly expressed in the endocardial cushions of the atrioventricular and outflow tract regions and in the atrioventricular, semilunar, and venous valves. This study raises the possibility that versican may be involved in specification of the ventricular chambers, in growth and fusion of the atrial and ventricular septa, and in the transformation from epithelium to mesenchyme that characterizes development of the endocardial cushions. Versican may be a key participant in cardiogenesis, responding to the many diffusible signals that mediate interactions between the developing endocardium and myocardium.