bluuebunny/crossref_metadata_2025 huggingface dataset:
Folate and Genetics
Authors: ROZEN RIMA
Published: November 2006

ABSTRACT: Inborn errors of folate/homocysteine metabolism are rare disorders that lead to a wide variety of developmental, neurological, and vascular complications; this group of disorders (homocystinurias) have been recognized for several decades. More recently, however, common mutations (or polymorphisms) in enzymes of folate metabolism have become identified as potential risk modifiers of several multifactorial disorders including neural tube defects, pregnancy complications, vascular disease, and cancer. The first and best characterized of this group of variants is an alanine‐to‐valine substitution at bp 677 of the enzyme methylenetetrahydrofolate reductase (MTHFR) which synthesizes the folate derivative for homocysteine remethylation to methionine. This variant, present in the homozygous state in 10% ‐ 15% of many North American, European, and Asian populations, results in mild hyperhomocysteinemia predominantly when folate status is low; this observation alludes to an increased requirement for folate in mutant individuals. The clinical impact of this variant, as well as a brief description of other variants in folate/homocysteine metabolism, will be discussed. In more recent work, we generated a mouse model with MTHFR deficiency, in order to address the genetic‐nutrient interactive effect and the biologic consequences of a disruption of folate metabolism. These mice have hyperhomocysteinemia, altered methylation, and enhanced utilization of choline/betaine to increase methionine biosynthesis. In addition, the mice appear to be quite useful as animal models for some of the above‐mentioned clinical disorders.
Plant productivity and soil nitrogen as a function of grazing, migration and fire in an African savanna
Authors: HOLDO RICARDO M. , HOLT ROBERT D. , COUGHENOUR MICHAEL B. , RITCHIE MARK E.
Published: November 2006

Herbivores can play a key role in affecting ecosystem function, but their direct and indirect effects are often confounded with each other and have rarely been dissected. Predictions for open systems, i.e. those with cross‐habitat nutrient fluxes and dispersal, may differ from those expected in closed systems, where no such transfers occur, but these differences have only recently begun to be characterized.

We present a theoretical model of plant productivity and soil nitrogen (N) based on the Serengeti ecosystem in order to investigate the interplay among herbivore movement, nutrient transport across habitats (spatial subsidies), the fire regime and the effects of herbivores on N cycling.

Model results suggest that the fire regime and herbivore migration are key determinants of primary productivity and fertility, and that the impact of these factors depends on grazing intensity. At low intensity, high grass biomass leads to extensive fires and N volatilization, but this effect is reduced at high grazing intensity. Without migration, the model predicts that primary productivity and fertility initially increase, then decline with increasing grazing intensity. Conversely, seasonal migration decouples the growing and grazing seasons, leading to a monotonic increase in productivity with grazing intensity. Cross‐habitat N transport has a relatively modest effect on N dynamics, and the magnitude of the seasonality effect outweighs the spatial subsidy effect.

Our model suggests that herbivores and fire may play key interactive roles in regulating producers and determining ecosystem functional properties in grazing systems, both through consumption and via indirect effects on nutrient availability. The direction and magnitude of these effects could potentially vary greatly among ecosystems with resident vs. migratory herbivores, suggesting that spatial coupling through animal movement can be important at both the population and ecosystem levels.

This study suggests that the degree to which trophic interactions influence ecosystem function may be strongly modulated by whether systems are open or closed. It also suggests that direct and indirect effects of consumers on their resources (top‐down effects) may be far more important than nutrient subsidies in open terrestrial systems.
Role of niche restrictions and dispersal in the composition of arbuscular mycorrhizal fungal communities
Authors: LEKBERG YLVA , KOIDE ROGER T. , ROHR JASON R. , ALDRICH‐WOLFE LAURA , MORTON JOSEPH B.
Published: November 2006

Metacommunity and neutral theory have reinvigorated the study of ‘niches’ and have emphasized the importance of understanding the influences of competition, abiotic factors and regional spatial processes in shaping communities.

We conducted a field survey to examine the effects of soil characteristics and distance on arbuscular mycorrhizal (AM) fungal communities of maize (Zea mays) in sand and clay soils. To address whether the field distributions of AM fungal species represented their fundamental or realized niches, we grew representative species of the two dominant genera, Glomus and Gigaspora, alone or together on Sorghum bicolor plants in sand, clay or a sand/clay mixture in the glasshouse.

In the field, soil characteristics and spatial structure accounted for significant proportions of the variation in community composition among sites, suggesting that both environmental variables and dispersal were important factors shaping AM fungal communities.

AM fungi in the family Glomeraceae occurred predominately in clay soils, whereas AM fungi in the family Gigasporaceae dominated in sand soils. Niche space of Glomeraceae was further partitioned by levels of soil organic carbon and nitrogen.

In the glasshouse, root colonization by Glomus was high in all three soils when grown in the absence of Gigaspora, indicating a broad fundamental niche. Root colonization by Gigaspora was negatively correlated with percentage clay when grown in the absence of Glomus, consistent with the low abundance of this family in clay soils in the field. When grown together, spore production of both Glomus and Gigaspora was significantly reduced only in the sand soil, indicating that competition could limit niches of both families in certain soil environments.

Our results suggest that AM fungal distributions are the product of environment, interspecific competition and regional spatial dynamics, emphasizing the importance of using a metacommunity perspective in community ecology.
Racial differences in treatment preferences: oral health as an example
Authors: Tilashalski Ken R. , Gilbert Gregg H. , Boykin Michael J. , Litaker Mark S.
Published: November 2006

Rationale, aims and objectives  Recent analyses from the Florida Dental Care Study found that response to a hypothetical scenario at baseline strongly predicted: (a) tooth loss during follow‐up; and (b) subsequent receipt of either a dental extraction or Root Canal Therapy (RCT). The scenario (‘CHOICE’) required choosing either to: (1) extract the tooth before even knowing the cost of treatments; (2) extract, but after knowing the cost of all treatments; or (3) have RCT despite knowing costs.

Objective  The purpose of this study was to identify factors associated with CHOICE and quantify their effects.

Methods  As part of the baseline phase of the study, 873 subjects with at least one tooth and who were 45 years or older participated for an interview and dental examination. A multinomial multivariable regression of CHOICE quantified effects due to hypothesized predictors.

Results  CHOICE was strongly associated with race (African‐Americans were significantly less likely to choose RCT). Results from the multivariable regression suggest that the race effect could be explained by racial differences in patient preference, treatment acceptability and ability to afford treatment.

Conclusions  There were substantial racial differences in treatment preference even in this hypothetical scenario where racial differences in patient–provider interaction and clinical factors were not relevant. Certain predisposing and enabling variables explained these racial differences in treatment preference.
Economic analysis for clinical practice – the case of 31 national consensus guidelines in the Netherlands
Authors: Niessen Louis W. , Grijseels Els , Koopmanschap Marc , Rutten Frans
Published: November 2006

Rationale, aims and objective Evidence on the cost‐effectiveness of health interventions in the development of practice guidelines has become of interest in many countries. Challenges are the quality of economic data, the use of cost‐effectiveness criteria, and the consensus process. Our paper aims to assess the quality and use of economic information in the formulation of consensus guidelines in a Dutch pilot programme and to recommend improvements.

Methods  Retrospective qualitative review of economic evaluations and formulated recommendations, using a checklist based on international standards.

Results The national programme to support the development of guidelines with economic analysis in multidisciplinary consensus groups run from 1998 to 2002. It has included 31 medical guidelines, addressing 23 conditions across seven International Classification of Diseases (ICD)‐disease groups. Experts in health technology assessment have participated in the guidelines groups. Economic information in all guidelines varies by all criteria in the level of evidence used. Information on quality‐adjusted life years gained is limited as is statistical analysis in most studies. Highest cost‐effectiveness ratios reported are between €20 000 and €30 000. However, there is no uniformity in the definitions of acceptable cost‐effectiveness ratios.

Conclusions Economic recommendations can be included in guidelines. Interaction between clinicians and health economists promotes a balance between medical and economic arguments. Among panellists there appears to be agreement on the level of the cost‐effectiveness ratios that is acceptable. It is recommended that economic analysis is used to strengthen the evidence‐base of guidelines. An evidence‐grading system should include the quality of economic evaluation. Roles of policymakers and providers need to be defined.
Using semantic differentials in fieldwork
Authors: Shields Linda
Published: November 2006

Rationale  A large project was undertaken to examine attitudes and opinions of health staff and parents about the care of hospitalized children in four countries. A simple scoring system, which allowed comparisons between results from each country, was needed to examine concepts under investigation.

Aims and objectives  This paper describes how, after trialling a range of methods, semantic differentials (SD) were found to be easy for the subjects to use. They translated well into other languages and provided scores which were easy to analyse and compare.

Results  Semantic differentials are based on a series of line scores using adjectives and their antonyms for a set of characteristics. They are a particularly useful method for fieldwork analysis, as they can be done by hand with no computer support.

Conclusions  Semantic differentials were found to be useful for cross‐cultural, quantitative studies of this kind. I discuss SDs, how they work, their trialling, reliability and validity and their usefulness in cross‐cultural research.
Treatment and survival from breast cancer: the experience of patients at South Australian teaching hospitals between 1977 and 2003
Authors: Luke Colin , Gill Grantley , Birrell Stephen , Humeniuk Vlad , Borg Martin , Karapetis Christos , Koczwara Bogda , Olver Ian , Penniment Michael , Pittman Ken , Price Tim , Walsh David , Kiat (Eric) Yeoh Eng , Roder David
Published: November 2006

Rationale  Treatment guidelines recommend a more conservative surgical approach than mastectomy for early stage breast cancer and a stronger emphasis on adjuvant therapy. Registry data at South Australian teaching hospitals have been used to monitor survivals and treatment in relation to these guidelines.

Aims and objectives  To use registry data to: (1) investigate trends in survival and treatment; and (2) compare treatment with guidelines.

Methods  Registry data from three teaching hospitals were used to analyse trends in primary courses of treatment of breast cancers during 1977–2003 (n = 4671), using univariate analyses and multiple logistic regression. Disease‐specific survivals were analysed using Kaplan–Meier product limit estimates and multivariable Cox proportional hazards regression.

Results  The 5‐year survival was 79.9%, but with a secular increase, reaching 83.6% in 1997–2003. The relative risk of death (95% confidence limits) was 0.74 (0.62, 0.88) for 1997–2003, compared with previous diagnoses, after adjusting for tumour node metastasis stage, grade, age and place of residence. Treatment changes included an increase in conservative surgery (as opposed to mastectomy) from 51.7% in 1977–1990 to 76.8% in 1997–2003 for stage I (P < 0.001) and from 31.1% to 52.2% across these periods for stage II (P < 0.001). Adjuvant radiotherapy also became more common (P < 0.001), with 20.6% of patients receiving this treatment in 1977–1990 compared with 60.7% in 1997–2003. Radiotherapy generally was more prevalent when conservative surgery was provided, although also relatively common in mastectomy patients when tumour diameters exceeded 50 mm or when there were four or more involved nodes. The proportion of patients receiving chemotherapy increased (P < 0.001), from 19.6% in 1977–1990 to 36.9% in 1997–2003, and the proportion having hormone therapy also increased (P < 0.001), from 34.3% to 59.4% between these periods.

Conclusions  Survivals appear to be increasing and treatment trends are broadly consistent with guideline directions, and the earlier research on which these recommendations were based.
Risk prediction for Down’s syndrome in young pregnant women using maternal serum biomarkers: determination of cut‐off risk from receiver operating characteristic curve analysis
Authors: Hwa Hsiao‐Lin , Ko Tsang‐Ming , Hsieh Fon‐Jou , Yen Ming‐Fang , Chou Kai‐Pei , Chen Tony Hsiu‐Hsi
Published: November 2006

Objective  The aim of this study was to establish a predictive model for Down’s syndrome using maternal age as well as maternal serum levels of alpha‐fetoprotein (AFP) and human chorionic gonadotropin (hCG), and to identify an optimal cut‐off risk in women under the age of 35 years to improve sensitivity.

Methods  Logistic regression models were utilized to predict fetal Down’s syndrome as a function of maternal age and logarithm of levels of AFP as well as hCG using training data of 20 pregnancies with fetal Down’s syndrome and 9730 unaffected pregnancies. Validation was performed using data of another nine affected pregnancies and 3496 unaffected pregnancies. Receiver operating characteristic (ROC) curves were plotted.

Results  Based on the newly established logistic regression equations, the optimal cut‐off risk from the ROC curve analysis was at 1:499, with a 17.8% false‐positive rate and a 90.0% sensitivity. A suboptimal cut‐off risk was estimated at 1:332, with a 12.0% false‐positive rate and an 80% sensitivity.

Conclusion  A predictive model for Down’s syndrome was developed using logistic regression. By ROC curve analysis and clinical consideration, the cut‐off risk for young pregnant women could be determined.
The clinical and cultural factors in classifying low back pain patients within Greece: a qualitative exploration of Greek health professionals
Authors: Billis Evdokia V. , McCarthy Christopher J. , Stathopoulos Ioannis , Kapreli Eleni , Pantzou Paulina , Oldham Jacqueline A.
Published: November 2006

Rationale, aims and objectives Identifying homogenous subgroups of low back pain (LBP) patients is considered a priority in musculoskeletal rehabilitation and is believed to enhance clinical outcomes. In order to achieve this, the specific features of each subgroup need to be identified. The aim of this study was to develop a list of clinical and cultural features that are included in the assessment of LBP patients in Greece, among health professionals. This ‘list’ will be, utilized in a clinical study for developing LBP subgroups.

Methods Three focus groups were conducted, each one comprising health professionals with homogenous characteristics and all coordinated by a single moderator. There were: 11 physiotherapists (PTs) with clinical experience in LBP patients, seven PTs specialized in LBP management, and five doctors with a particular spinal interest.The focus of discussions was to develop a list of clinical and cultural features that were important in the examination of LBP. Content analysis was performed by two researchers.

Results Clinicians and postgraduates developed five categories within the History (Present Symptoms, History of Symptoms, Function, Psychosocial, Medical History) and six categories within the Physical Examination (Observation, Neurological Examination, Active and Passive Movements, Muscle Features and Palpation). The doctors identified four categories in History (Symptomatology, Function, Psychosocial, Medical History) and an additional in Physical Examination (Special Tests). All groups identified three cultural categories; Attitudes of Health Professionals, Patients’ Attitudes and Health System influences.

Conclusion An extensive Greek ‘list’ of clinical and cultural features was developed from the groups’ analysis. Although similarities existed in most categories, there were several differences across the three focus groups which will be discussed.
Phylogeography of the green turtle, Chelonia mydas, in the Southwest Indian Ocean
Authors: BOURJEA J. , LAPÈGUE S. , GAGNEVIN L. , BRODERICK D. , MORTIMER J. A. , CICCIONE S. , ROOS D. , TAQUET C. , GRIZEL H.
Published: November 2006

Patterns of mitochondrial DNA (mtDNA) variation were used to analyse the population genetic structure of southwestern Indian Ocean green turtle (Chelonia mydas) populations. Analysis of sequence variation over 396 bp of the mtDNA control region revealed seven haplotypes among 288 individuals from 10 nesting sites in the Southwest Indian Ocean. This is the first time that Atlantic Ocean haplotypes have been recorded among any Indo‐Pacific nesting populations. Previous studies indicated that the Cape of Good Hope was a major biogeographical barrier between the Atlantic and Indian Oceans because evidence for gene flow in the last 1.5 million years has yet to emerge. This study, by sampling localities adjacent to this barrier, demonstrates that recent gene flow has occurred from the Atlantic Ocean into the Indian Ocean via the Cape of Good Hope. We also found compelling genetic evidence that green turtles nesting at the rookeries of the South Mozambique Channel (SMC) and those nesting in the North Mozambique Channel (NMC) belong to separate genetic stocks. Furthermore, the SMC could be subdivided in two different genetic stocks, one in Europa and the other one in Juan de Nova. We suggest that this particular genetic pattern along the Mozambique Channel is attributable to a recent colonization from the Atlantic Ocean and is maintained by oceanic conditions in the northern and southern Mozambique Channel that influence early stages in the green turtle life cycle.
Population genetic signatures of diffuse co‐evolution between leaf‐cutting ants and their cultivar fungi
Authors: MIKHEYEV A. S. , MUELLER U. G. , BOOMSMA J. J.
Published: November 2006

Switching of symbiotic partners pervades most mutualisms, despite mechanisms that appear to enforce partner fidelity. To investigate the interplay of forces binding and dissolving mutualistic pairings, we investigated partner fidelity at the population level in the attine ant–fungal cultivar mutualism. The ants and their cultivars exhibit both broad‐scale co‐evolution, as well as cultivar switching, with short‐term symbiont fidelity maintained by vertical transmission of maternal garden inoculates via dispersing queens and by the elimination of alien cultivar strains. Using microsatellite markers, we genotyped cultivar fungi associated with five co‐occurring Panamanian attine ant species, representing the two most derived genera, leaf‐cutters Atta and Acromyrmex. Despite the presence of mechanisms apparently ensuring the cotransmission of symbiont genotypes, different species and genera of ants sometimes shared identical fungus garden genotypes, indicating widespread cultivar exchange. The cultivar population was largely unstructured with respect to host ant species, with only 10% of the structure in genetic variance being attributable to partitioning among ant species and genera. Furthermore, despite significant genetic and ecological dissimilarity between Atta and Acromyrmex, generic difference accounted for little, if any, variance in cultivar population structure, suggesting that cultivar exchange dwarfs selective forces that may act to create co‐adaptive ant–cultivar combinations. Thus, binding forces that appear to enforce host fidelity are relatively weak and pairwise associations between cultivar lineages and ant species have little opportunity for evolutionary persistence. This implicates that mechanisms other than partner fidelity feedback play important roles in stabilizing the leafcutter ant–fungus mutualism over evolutionary time.
Landscape‐scale genetic variation in a forest outbreak species, the mountain pine beetle (Dendroctonus ponderosae)
Authors: MOCK K. E. , BENTZ B. J. , O’NEILL E. M. , CHONG J. P. , ORWIN J. , PFRENDER M. E.
Published: November 2006

The mountain pine beetleDendroctonus ponderosaeis a native species currently experiencing large‐scale outbreaks in western North American pine forests. We sought to describe the pattern of genetic variation across the range of this species, to determine whether there were detectable genetic differences betweenD. ponderosaeoccupying different host trees in common localities, and to determine whether there was molecular evidence for a past demographic expansion. Using a combination of amplified fragment length polymorphism (AFLP) and mitochondrial sequencing analyses, we found evidence of genetic structuring among populations that followed a broad isolation‐by‐distance pattern. Our results suggest that the geographical pattern of gene flow follows the core distribution of the principalD. ponderosaehost species, around rather than across the Great Basin and Mojave Deserts. Patterns of haplotype diversity and divergence were consistent with a range‐wide population expansion. This signal was particularly pronounced in the northern part of the species’ range, where outbreak activity is currently increasing. Using AFLP markers, we were unable to detect significant differences among groups of insects sampled from different host trees in common locations. Incidentally, we found that a large proportion of the polymorphic AFLP markers were gender‐specific, occurring only in males. While we did not include these markers in our analyses, this finding warrants further investigation.
Maturation of the 5′ end of Bacillus subtilis 16S rRNA by the essential ribonuclease YkqC/RNase J1
Authors: Britton Robert A. , Wen Tingyi , Schaefer Laura , Pellegrini Olivier , Uicker William C. , Mathy Nathalie , Tobin Crystal , Daou Roula , Szyk Jacek , Condon Ciarán
Published: November 2006

Functional ribosomal RNAs are generated from longer precursor species in every organism known. Maturation of the 5′ side of 16S rRNA in Escherichia coli is catalysed in a two‐step process by the cooperative action of RNase E and RNase G. However, many bacteria lack RNase E and RNase G orthologues, raising the question as to how 16S rRNA processing occurs in these organisms. Here we show that the maturation of Bacillus subtilis 16S rRNA is also a two‐step process and that the enzyme responsible for the generation of the mature 5′ end is the widely distributed essential ribonuclease YkqC/RNase J1. Depletion of B. subtilis of RNase J1 results in an accumulation of 16S rRNA precursors in vivo. The precursor species are found in polysomes suggesting that they can function in translation. Mutation of the predicted catalytic site of RNase J1 abolishes both 16S rRNA processing and cell viability. Finally, purified RNase J1 can correctly mature precursor 16S rRNA assembled in 70S ribosomes, showing that its role is direct.
Changes of initiation mass and cell dimensions by the ‘eclipse’
Authors: Zaritsky Arieh , Vischer Norbert , Rabinovitch Avinoam
Published: November 2006

The minimum time (E) required for a new pair of replication origins (oriCs) produced upon initiating a round of replication to be ready to initiate the next round after one cell mass doubling, the ‘eclipse’, is explained in terms of a minimal distance (lmin) that the replication forks must move away from oriC before oriCs can ‘fire’ again. In conditions demanding a scheduled initiation event before the relative distance lmin/L0.5 (L being the total chromosome length) is reached, initiation is presumably delayed. Under such circumstances, cell mass at the next initiation would be greater than the usual, constant Mi (cell mass per copy number of oriC) prevailing in steady state of exponential growth. This model can be tested experimentally by extending the replication time C using thymine limitation at short doubling times τ in rich media to reach a relative eclipse E/C < lmin/L0.5. It is consistent with results obtained in experiments in which the number of replication ‘positions’n (= C/τ) is increased beyond the natural maximum, causing the mean cell size to rise continuously, first by widening, then by lengthening, and finally by splitting its poles. The consequent branching is associated with casting off a small proportion of normal‐sized cells and lysing DNA‐less cells. Whether or how these phenomena are related to peptidoglycan composition and synthesis are moot questions.
Structural Evidence for a New IgG1 Antibody Sequence Allele of Cattle
Authors: Saini S. S. , Farrugia W. , Muthusamy N. , Ramsland P. A. , Kaushik A. K.
Published: November 2006

Analysis of the heavy‐chain gene (pTGHC9907) encoding a bovine IgG1 antibody against bovine herpes virus type 1 (BHV‐1) isolated from a Holstein cow has led to the identification of a new IgG1 sequence allele. A comparison of nucleotide sequence of pTGHC9907 with the IgG1a (clone 2) and IgG1b (clone 8.10) sequence variants and unclassified IgG1 cDNA sequence (clone 8.75) has revealed significant differences in the hinge region spanning codons 216–230. The Thr224 and Thr226 of IgG1a were replaced with Arg224 and Pro226, while both Thr218 and Pro224 of IgG1b were substituted with Arg with deletion of Ser225 in HB9907 antibody. Additional amino acid substitutions were noted in the CH1 (positions 190, 192), CH2 (position 281) and CH3 (position 402) exons. Thus, the polymorphic sites occurred in all constant domains, but were clustered in the hinge region of IgG1. Examination of a three‐dimensional model of the HB9907 heavy chain revealed that all sequence variations were on the surface of the IgG and are possible targets for recognition by antisera and effector molecules such as cellular adhesion molecules. The presence in the CH1 domain of a repeating motif of Pro–Ala–Ser–Ser indicated a potential structure‐enhancing function and a role in cellular adhesion and migration. Replacement of Thr with Arg residues within the hinge was predicted to have a dual effect of reducing the number of O‐linked glycosylation sites and increasing the susceptibility to degradation by protease‐secreting bacteria of the hinge region. As unclassified IgG1 cDNA sequence (clone 8.75) is structurally distinct from other variants, it is also classified as IgG1d. Collectively, these observations support the identification of a new allotypic variant of bovine IgG1, designated as IgG1c that is distinct in both sequence and structure from the known sequence variants.
Partial Depletion of CD69low‐expressing Natural Regulatory T Cells with the Anti‐CD25 Monoclonal Antibody PC61
Authors: McNeill A. , Spittle E. , Bäckström B. T.
Published: November 2006

The role CD4+ CD25+ regulatory T cells (Treg) play in modulating the immune response has been investigated extensively over recent years. Much of the work to date has used the activation marker CD25 to define, enrich and deplete Treg. However, the identification of FoxP3 as a definitive marker of Treg has allowed us to study the effect of monoclonal antibodies against CD25 on regulatory T‐cell populations. Recently, published data have indicated that Treg are inactivated, not depleted, through treatment with anti‐CD25 monoclonal antibody. Using FoxP3‐Green fluorescent protein reporter mice, we show that treatment with the CD25 MoAb PC61 depleted a subpop ulation of Treg. The depleted Treg population expressed low levels of the CD69 marker, indicating an inactive phenotype. In addition, PC61 treatment altered the function of the remaining regulatory T‐cell population, preventing their ability to modulate autoimmune diseases. Thus, our results have important implications with regard to interpreting experimental outcomes from in vivo anti‐CD25 treatments.
Contourite drifts, moats and channels in the Upper Cretaceous chalk of the Danish Basin
Authors: SURLYK FINN , LYKKE‐ANDERSEN HOLGER
Published: November 2006

During the Late Cretaceous, high global sea‐level meant that most of the NW European craton was flooded by the deep epeiric ‘chalk sea’. The classical paradigm for chalk deposition envisages a quiet rain of minute skeletal debris of coccolithophorid algae and other pelagic organisms deposited as horizontal, flat‐lying pelagic oozes with local redeposition by slumps, slides and debris flows along faults and other structural features. Seismic data from the Danish Basin and elsewhere necessitate a revision of this paradigm. These demonstrate that the chalk sea floor had a considerable relief, commonly of more than a hundred metres amplitude, comprising moats, drifts, mounds and channels. Seismic sections from the Kattegat sea illustrate the development in the Maastrichtian of a deep moat adjacent to a topographic ridge formed over the inverted NW–SE‐trending Sorgenfrei–Tornquist Zone. The moat was up to 120 m deeper than its SW flank which was formed by an internally complex elongate drift, up to 20 km wide with an estimated length ofca200 km. Smaller mound‐like features, channels and clinoform beds are superimposed on the large‐scale relief. The sea floor relief is interpreted to have formed in response to persistent bottom currents, flowing parallel to bathymetric contours. The initial build‐up of the broad, gently convex‐up sheeted drift was controlled by relatively low‐velocity bottom currents. The region of highest current velocity was gradually shifted NE‐wards towards the inversion zone ridge, resulting in the formation of the deep moat flanked by the elongate drift. The current is interpreted to have flowed from the SE towards NW on the basis of the internal architecture of the elongate drift and the NW‐ward branching and decrease in moat relief. The architecture and morphology of the moat drift and other features of the chalk sea floor are in all aspects similar to contourite systems of modern continental margins. It is accordingly proposed that the fundamental physical oceanographic concept – contour currents and their resulting contourite drifts – is extended to include the deep epeiric seas which covered NW Europe during the Late Cretaceous.
Integrating outcrop data and forward computer modelling to unravel the development of a Messinian carbonate platform in SE Spain (Sorbas Basin)
Authors: CUEVAS CASTELL JOSÉ M. , BETZLER CHRISTIAN , RÖSSLER JOCHEN , HÜSSNER HANSMARTIN , PEINL MARK
Published: November 2006

Geological mapping, definition of facies distributions and reconstruction of platform‐interior growth geometries of the Messinian Cariatiz carbonate platform (Sorbas basin, South Spain), were performed to evaluate the controlling factors in platform growth and to test a 3‐D computer simulation program. For the simulation with the program REPRO, five platform‐related facies were modelled: (1) the reef crest facies by the numerical solution of a Fisher equation; (2) the lagoonal facies by a function of water depth‐dependent carbonate production; (3) the proximal and middle slope facies (breccia and block facies, calcarenite facies) by a subroutine simulating gravity‐driven particle export from the reef crest; (4) a distal slope; and (5) a basinal facies by a pelagic rain function. Development of a fan delta conglomeratic system is simulated by using a siliciclastic point source and gravity‐driven particle redistribution. A best fit between the observed platform growth geometries and modelling results is achieved by assuming that high‐frequency sea‐level changes superimposed onto a longer term sea‐level fall controlled platform growth. For the modelling, a relative sea‐level curve was reconstructed, which is based on a deep‐sea benthic foraminiferal stable oxygen isotope record at ODP Site 926 with a 45 m eustatic sea‐level fall, and a tectonic uplift component of 20 m. The consistency of 3‐D simulation results is corroborated by the coral growth rates provided by the Fisher‐equation subroutine. These rates of 2–8 mm year−1 compare well to the coral growth rates in Recent fringing reefs. We propose that during the early stage of platform evolution the high‐frequency fluctuations were obliquity‐modulated precessional cycles, whereas precessional cycles control later stages of platform growth. REPRO provides a separate visualization of the different facies bodies as a function of time and space, showing the intrinsic pattern of facies distribution in the platform. This is the result of a combination of platform growth and syndepositional subaerial erosion. For example, only the youngest stages of reef framework facies in the development of the Cariatiz carbonate platform are preserved.
Identification of PAD2 as a γ‐glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis
Authors: Parisy Vincent , Poinssot Benoit , Owsianowski Lucas , Buchala Antony , Glazebrook Jane , Mauch Felix
Published: November 2006

The Arabidopsis pad2‐1 mutant belongs to a series of non‐allelic camalexin‐deficient mutants. It was originally described as showing enhanced susceptibility to virulent strains of Pseudomonas syringae and was later shown to be hyper‐susceptible to the oomycete pathogen Phytophthora brassicae (formerly P. porri). Surprisingly, in both pathosystems, the disease susceptibility of pad2‐1 was not caused by the camalexin deficiency, suggesting additional roles of PAD2 in disease resistance. The susceptibility of pad2‐1 to P. brassicae was used to map the mutation to the gene At4g23100, which encodes γ‐glutamylcysteine synthetase (γ‐ECS, GSH1). GSH1 catalyzes the first committed step of glutathione (GSH) biosynthesis. The pad2‐1 mutation caused an S to N transition at amino acid position 298 close to the active center. The conclusion that PAD2 encodes GSH1 is supported by several lines of evidence: (i) pad2‐1 mutants contained only about 22% of wild‐type amounts of GSH, (ii) genetic complementation of pad2‐1 with wild‐type GSH1 cDNA restored GSH production, accumulation of camalexin in response to P. syringae and resistance to P. brassicae and P. syringae, (iii) another GSH1 mutant, cad2‐1, showed pad2‐like phenotypes, and (iv) feeding of GSH to excised leaves of pad2‐1 restored camalexin production and resistance to P. brassicae. Inoculation of Col‐0 with P. brassicae caused a coordinated increase in the transcript abundance of GSH1 and GSH2, the gene encoding the second enzyme in GSH biosynthesis, and resulted in enhanced foliar GSH accumulation. The pad2‐1 mutant showed enhanced susceptibility to additional pathogens, suggesting an important general role of GSH in disease resistance of Arabidopsis.
Role of plant CBP/p300‐like genes in the regulation of flowering time
Authors: Han Soon‐Ki , Song Ju‐Dong , Noh Yoo‐Sun , Noh Bosl
Published: November 2006

CREB‐binding protein (CBP) and its homolog p300 possess histone acetyltransferase activity and function as key transcriptional co‐activators in the regulation of gene expression that controls differentiation and development in animals. However, the role of CBP/p300‐like genes in plants has not yet been elucidated. Here, we show that Arabidopsis CBP/p300‐like genes promote flowering by affecting the expression of a major floral repressor FLOWERING LOCUS C (FLC). Although animal CBP and p300 generally function as co‐activators, Arabidopsis CBP/p300‐like proteins are required for the negative regulation of FLC. This CBP/p300‐mediated FLC repression may involve reversible protein acetylation independent of histone modification within FLC chromatin.
CD47 is expressed at normal levels in patients with autoimmune haemolytic anaemia and/or immune thrombocytopenia
Authors: Ahrens N. , Pagenkopf C. , Kiesewetter H. , Salama A.
Published: November 2006

summary CD47 deficiency results in lethal autoimmune haemolytic anaemia (AIHA) and mild spontaneous thrombocytopenia in non‐obese diabetic mice. It is unknown whether CD47 has an impact on AIHA of the warm type or autoimmune thrombocytopenia (ITP) in humans.

Healthy blood donors (n= 11), patients with AIHA (n= 13), patients with ITP (n= 18) and one patient with Rhnull phenotype were investigated. CD47 expression on red blood cells (RBC), platelets, granulocytes and lymphocytes and in plasma was determined by quantitative flow cytometry.

All types of blood cells studied were found to carry CD47. Although CD47 expression on Rhnull RBCs was decreased, there was no significant difference between CD47 expression on RBCs of healthy blood donors and on those of patients with AIHA or ITP. Similarly, CD47 was detectable in the plasma of the studied subjects.

No evidence for a pathogenetic role of CD47 in autoimmune haemolysis or thrombocytopenia in humans could be demonstrated.
Field evaluation of four novel enzyme immunoassays for Chagas’ disease in Venezuela blood banks: comparison of assays using fixed‐epimastigotes, fixed‐trypomastigotes or trypomastigote excreted–secreted antigens from two Trypanosoma cruzi strains
Authors: Berrizbeitia M. , Ndao M. , Bubis J. , Gottschalk M. , Aché A. , Lacouture S. , Medina M. , Ward B. J.
Published: November 2006

summary Many serological tests have been developed for the diagnosis of Chagas’ disease, but few have been subjected to a rigorous field evaluation. We have recently described several novel enzyme immunoassays (EIAs) based on fixed‐whole organisms or trypomastigote excretory–secretory antigens (TESA) from different Trypanosoma cruzi strains (Tulahuen or Brazil). This study evaluated the most promising of these novel assays (e.g. fixed‐epimastigotes, fixed‐trypomastigotes, TESA Brazil and TESA Tulahuen antigens) in a field study of Venezuelan blood bank specimens. The assays were tested in an operator‐blinded fashion using 2038 blood bank samples obtained from low and high T.cruzi prevalence regions of Venezuela (n= 1050 and n= 988 from Bolivar and Portuguesa states, respectively). Based on National Laboratory for Chagas Immunodiagnosis (NLCI) ‘gold standard’ results, all novel EIAs were superior to the commercial kit currently used in Venezuela, achieving 100% sensitivity and >99% specificity at optimal cut‐off values. The novel assays identified seven false‐negative samples compared with the routine screening performed by the Venezuelan blood bank although two samples were also misclassified as positive. Minor differences in the performance of the four novel assays were observed at lower arbitrary cut‐off values. This study confirms the potential utility of both the fixed‐organism and the TESA‐based assays in the diagnosis of T.cruzi infection.
Distribution of hepatitis C virus genotypes in beta‐thalassaemic patients from Northern India
Authors: Chakravarti A. , Verma V.
Published: November 2006

summary Multitransfused beta‐thalassaemic patients constitute a population having a higher prevalence of hepatitis C virus (HCV) infection because of its transmission from infected blood collected during seronegative window period. HCV genotyping in thalassaemic patients is mainly useful for the clinical management of the patients and for facilitating decisions on therapy. Thus, the aim of the present study was to identify the genotypes that are prevalent in thalassaemic patients and to correlate these with gender, age, number of blood transfusions and the liver function test profiles. Reverse transcription–polymerase chain reaction (RT‐PCR) was carried out in 80 beta‐thalassaemic patients (58 men and 22 women) for detection of HCV RNA who were seronegative for hepatitis B virus or human immunodeficiency virus antibodies. HCV genotyping was carried out by restriction fragment length polymorphism (RFLP) method of Chinchai et al. Type‐specific PCR followed by direct sequencing was also used to confirm the mixed‐genotype infection. Among the 80 thalassaemic patients, 20 and eight patients were infected with genotypes 3 and 1, respectively, whereas two cases had infection with HCV genotype1c/5a. The serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were found to be significantly altered between the two groups of HCV‐infected and noninfected thalassaemic patients. No significant correlation was observed between genotypes when compared with gender, age and number of blood transfusions, except significantly higher level of ALP in genotype 1 than in genotype 3. Genotype 3 alone was the predominant type in beta‐thalassaemic patients, with approximately 45% being infected with mixed type. Hence, detection of HCV RNA would help in decreasing the transmission of HCV‐infected blood collected during the seronegative window period, whereas determination of genotypes would provide help in adoption of different treatment policies for better management of thalassaemic patients.
Using schoolchildren's reports of bed net use monitored by schoolteachers as a proxy of community coverage in malaria endemic areas of Uganda
Authors: Ndyomugyenyi Richard , Kroeger Axel
Published: November 2006

Objective  Community‐based information on the delivery and use of health interventions is important to monitor the effectiveness of the Roll Back Malaria programme. However, community surveys to determine coverage for insecticide‐treated bed nets are time‐consuming and costly. We wanted to assess whether schoolchildren's reports of household ownership of a bed net and coverage among high‐risk groups monitored by schoolteachers through a questionnaire could be used as a proxy of household ownership of bed net and coverage at community level, for routine monitoring of malaria control programmes.

Method  3602 schoolchildren in 39 randomly selected schools and 2798 heads of households in 39 villages were interviewed about their use of either insecticide‐treated or untreated bed nets.

Results  The overall household ownership of any kind of bed net was 35% in school surveys and 31% in household surveys (P < 0.001). Household ownership of insecticide‐treated nets was 23% and 22%, respectively (P = 0.4); household ownership of untreated nets was 15% and 9%, respectively (P < 0.001). There was significant correlation between estimates of any bed net and treated net ownership based on household surveys and estimates based on school surveys (P < 0.01 for both).

Conclusions  In areas with high school attendance rates, schoolchildren's report of bed net use monitored by schoolteachers through a questionnaire could give a good approximation of household ownership of bed net at community level with about ±5% difference between community and school surveys. However, further operational research is required to investigate how the feasibility of large‐scale implementation might be, by sending the questionnaire to the schools through routine channels and by independent handling by the school administration and teachers.
Successful cardiac transplantation in Barth syndrome – single‐centre experience of four patients
Authors: Mangat Jasveer , Lunnon‐Wood Tracy , Rees Philip , Elliott Martin , Burch Michael
Published: November 2006

Abstract:  We describe four patients with Barth syndrome who have undergone successful orthotopic heart transplantation. Patients are one, seven, 12.5 and 14.7 yr post‐transplantation. One episode of severe infection occurred. Renal dysfunction and coronary allograft vasculopathy do not appear accelerated over non‐Barth patients. Despite withholding purine synthesis inhibitors, these patients have not demonstrated an increased rate of rejection.
Bone marrow transplantation in children with severe aplastic anemia using a conditioning regimen containing 3 Gy of total body irradiation, cyclophosphamide with or without antithymocyte globulin
Authors: Inagaki Jiro , Nagatoshi Yoshihisa , Kawano Yoshifumi , Saito Yusuke , Takahashi Daijiro , Nagayama Jun , Shinkoda Yuichi , Hirata Hideki , Okamura Jun
Published: November 2006

Abstract:  We have employed the 3 Gy toal body irradiation (TBI) containing conditioning regimen to bone marrow transplantation (BMT) for severe aplastic anemia (SAA) in pediatric patients irrespective of donor type since March 1986. The outcome of BMT for 17 SAA patients is favorable. Eight patients received BMT from human leukocyte antigen matched‐related donors (MRD) and nine received BMT from alternative donors. The conditioning regimen consisted of 3‐Gy TBI and cyclophosphamide of 200 mg/kg in the BMT from MRD. In the case of BMT from alternative donor, antithymocyte globulin 10 mg/kg was added to the regimen. Fifteen of 17 patients (88%) engrafted on median of day 18 (range, 11–26) and all 13 evaluable patients showed complete donor chimerism by median 30 (range, 13–47) days after BMT. Fourteen patients have survived with a median follow‐up of 67 (range, 2–228) months and the probability of survival was 81.9% (95% CI, 63.3–100%). No late complications including second malignancies caused by TBI have been observed and all three female patients have regular menstruation. In conclusion, TBI of 3 Gy appears to be an appropriate dose regarding to ensure engraftment and avoid the risk of late adverse event for SAA patients.
Subclinical cytomegalovirus and Epstein–Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation
Authors: Li Li , Chaudhuri Abanti , Weintraub Lauren A. , Hsieh Frank , Shah Sheryl , Alexander Steven , Salvatierra Oscar , Sarwal Minnie M.
Published: November 2006

Abstract:  Post‐transplant clinical disease with cytomegalovirus (CMV) and Epstein–Barr virus (EBV) is a known risk factor for graft dysfunction and lymphoproliferation. We postulate that subclinical, asymptomatic viremia also adversely impacts outcomes, and may warrant re‐assessment of current monitoring and antiviral prophylaxis protocols. A single‐center study was conducted on 102 pediatric (51 steroid‐free and 51 matched steroid‐based historical controls). Quantitative viral loads were serially monitored and correlated with outcome measures. Overall, the incidence of CMV and EBV clinical disease was 5% (1% CMV and 4% EBV); however, the incidence of subclinical viremia was 44% (12.7% CMV, 38.2% EBV, 6.9% CMV + EBV). Risk factors for subclinical viremia were EBV naivety (p = 0.07), age less than five yr (p = 0.04), lack of prophylaxis (p = 0.01), and steroid usage (p = 0.0007). Subclinical viremia was associated with lower three‐yr graft function (p = 0.03), increased risk of acute rejection (odds ratio 2.07; p = 0.025), hypertension (p = 0.04), and graft loss (p = 0.03). Subclinical asymptomatic CMV and EBV viremia is a risk factor for graft injury and loss. These findings support the need for aggressive, serial viral monitoring to better determine the appropriate length of post‐transplant antiviral prophylaxis, and to determine the effect of immunosuppression protocols on the development of viremia.