bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of the critical care assistant role within an acute NHS Trust Critical Care Unit
Authors: McGloin Sarah , Knowles Judie
Published: September 2010

This study provides an evaluation of a training programme designed for developing six critical care assistants to work alongside registered nurses to care for patients within the critical care environment. The programme was run as a pilot funded from the Department of Health's ‘critical care bid’. At 18 months long, the programme incorporated a foundation programme, and National Vocational Qualification (NVQ) level 3 in care and adapted Operating Department Practitioner (ODP) NVQ units. Six critical care assistants successfully completed the programme; however, they all then left the unit to undertake further study for pre‐registration nursing qualifications. Upon evaluation, a number of key issues were identified. Clear definition of the critical care assistants's role is essential as are dedicated practice development staff, who focus purely on developing the critical care assistant role. More importantly, however, with such key changes in the staffing structure within critical care units, appropriate change management techniques should be employed, ensuring that all staff contributing to the training and development are fully involved from the start.
Implementing a protocol for weaning patients off mechanical ventilation
Authors: Goodman Sheila
Published: September 2010

Weaning patients from ventilation can be a costly and time‐consuming intervention. This article describes how a protocol was designed and introduced into the critical care unit of a district general hospital in 2003. A step‐by‐step approach was used based on that outlined by the Modernisation Agency and The National Institute for Clinical Excellence. The purpose of the project was to improve the weaning process in the unit by devising a protocol, which would give structure to weaning and help maintain continuity. It was hoped that the changes in practice would also reduce ventilator time and improve patient outcomes. A multi‐professional group interested in weaning worked together to formulate a protocol, which was duly implemented into the unit. After implementation, the protocol was audited and subsequently adopted by the unit. Although it was agreed that the structure and the continuity of weaning had improved, reducing weaning times and patient outcomes was difficult to measure. This article explains how the protocol came to be written and how it was implemented into the unit.
A new valve for draw‐over anaesthesia*
Authors: Payne S. , Tully R. , Eltringham R.
Published: September 2010

The Diamedica non‐rebreathing valve has been developed for use in draw‐over anaesthesia and can be positioned at the common gas outlet. Its performance was evaluated against the Laerdal, Ruben and Ambu® valves under laboratory conditions. Valve resistance during inspiration and expiration was simulated over a range of constant flow conditions. During flows ranging from 5 to 45 l.min−1, the Diamedica and Ruben valves exhibited a negligible resistance of < 150 Pa, with the Laerdal and Ambu valves achieving resistance of < 200 Pa. To assess the effects of sterilisation, this procedure was repeated following autoclaving, after which the Diamedica valve exhibited resistance to flow of < 150 Pa at 25 l.min−1 for inlet resistance and 35 l.min−1 for outlet resistance. The Diamedica, Ambu and Laerdal valves demonstrated resistance of < 100 Pa when saturated with water, while the Ruben valve exhibited resistance > 500 Pa.
F8 and F9 mutations fail to co‐segregate in a family with co‐incident haemophilia A and B
Authors: SIDDIQ S. , MORSE C. , GOODEVE A. , PANAYI M. , TAIT R. C. , MUMFORD A.
Published: September 2010

Summary.  Haemophilia A and B in one individual may arise from co‐incident inheritance of independent mutations in the F8 and F9 genes. However, this association is rare and has been studied poorly at a genetic level. We report a male patient with abnormal bleeding and reduced factor VIII:C (26 IU dL−1) and factor IX:C (35 IU dL−1). This index case harboured a F8 c.979C>G transversion (predictive of p.Leu327Val) and a F9 c.845A>G transition (predictive of p.His282Arg) which have been previously associated with mild haemophilia A and B, respectively. Identical F8 and F9 mutations were identified in the mother and maternal grandmother. However, an affected maternal uncle showed only the F8 c.979C>G mutation, indicating haemophilia A alone. The sister of the index case was heterozygous only for F9 c.845A>G, indicating carriership of haemophilia B alone. The non‐Mendelian inheritance of F8 c.979C>G and F9 c.845A>G in this kindred is consistent with recombination between F8 and F9 and illustrates the large recombination distance between these loci. Recognition of this phenomenon was essential for accurate genetic counselling in this kindred.
Alterations of 9p21 analysed by FISH and MLPA distinguish atypical spitzoid melanocytic tumours from conventional Spitz’s nevi but do not predict their biological behaviour
Authors: Cesinaro Anna Maria , Schirosi Laura , Bettelli Stefania , Migaldi Mario , Maiorana Antonio
Published: September 2010

Cesinaro A M, Schirosi L, Bettelli S, Migaldi M & Maiorana A (2010) Histopathology 57, 515–527 Alterations of 9p21 analysed by FISH and MLPA distinguish atypical spitzoid melanocytic tumours from conventional Spitz’s nevi but do not predict their biological behaviour

Aim:  The aim of this study was to investigate whether 9p21 status influence the prognosis of the spitzoid melanocytic tumours, peculiar lesions whose biological behaviour cannot be predicted by histopathological criteria alone.

Methods and results:  Twenty‐eight atypical spitzoid tumours, 12 conventional Spitz’s nevi and one congenital Spitz’s nevus were studied by fluorescent in‐situ hybridization (FISH) and multiple ligation‐dependent probe amplification (MLPA) for the presence of 9p21 deletion. The 28 patients were aged 3–56 years (mean 32, median 35), and follow‐up ranged between 4 and 156 months (mean 51, median 48). Eight patients (28.5%) experienced lymph node metastasis (three cases with macrometastasis and five with micrometastasis). Of those with macrometastasis, two are alive after 159 and 26 months, whereas a third developed widespread metastases and died after 26 months. All of the other patients are alive. Statistically, the thickness (P = 0.01) and the diameter (P = 0.009) of the lesions significantly correlated with metastasis. Deletion of 9p21 by FISH analysis was observed in eight spitzoid tumours (28.5%), and MLPA demonstrated alterations of 9p21, particularly deletion of CDKN2A, in the same lesions, whereas all Spitz’s nevi, except the congenital one, were of unaltered 9p21 status (P < 0.0001). Deletion of 9p21/CDKN2A did not correlate with the presence of metastasis.

Conclusion:  Alterations at 9p21 locus are significantly more frequent in spitzoid tumours than in Spitz’s nevi, but do not predict their biological behaviour.
Genome size and organization in the ixodid tick Amblyomma americanum (L.)
Authors: Palmer M. J. , Bantle J. A. , Guo Xiaoping , Fargoxy1 W. Scott
Published: September 2010

We used DNA reassociation kinetics to determine genome size and organization in the ixodid tick Amblyomma americanum. We calculated the genome size of A. americanum to be approximately 1.08 pg or 1.04 × 109 base pairs and to consist of 35.8% unique DNA, 4.2% foldback sequences, 17.9% highly repetitive sequences, and 42.1% moderately repetitive sequences. Comparison of the reassociation kinetics of long and short fragments revealed repetitive sequences to be distributed in a pattern of long period interspersion, a feature that, to date, has been associated with arthropod genomes that lack a high percentage of repetitive DNA.
The use of Percoll gradients for the preparation of subpopulations of human spermatozoa
Authors: Arcidiacono A. , Walt H. , Campana A. , Balerna M.
Published: September 2010

Centrifugation of human spermatozoa on BWW‐ or HEPES‐Krebs‐Ringer‐buffered media containing Percoll as a method to prepare pure gamete populations or subpopulations has been studied in detail. Application of this technique (Gorus & Pipeleers 1981) allowed us to obtain uncontaminated, motile spermatozoa and, after a subsequent Percoll gradient step, resulted in the enrichment of motile cells able to readily penetrate in vitro into AB‐serum filled capillaries. The gradient sedimentation patterns of 25 different sperm samples with normal seminal parameters were found to be strongly influenced by the characteristics of the sample itself and also by the buffer used for filtration. However, the present study also revealed that ultrastructural changes and the release of intraspermatozoal enzymes were induced by the procedure. It is concluded that, although of interest clinically, the Percoll filtration technique in its present form is probably of limited value for cell biological and/or ultrastructural studies.
Association between seminal plasma carnitine and sperm mitochondrial enzymatic activities
Authors: Ruiz‐Pesini Eduardo , Alvarez Enrique , Enríquez José Antonio , López‐Pérez Manuel J.
Published: September 2010

Cellular parameters of the seminogram have been previously shown to correlate with L‐carnitine concentration in the seminal fluid. Carnitine is involved in a variety of metabolic processes playing an important role in maintaining an active oxidative phosphorylation (OXPHOS). Recently, we have found a significant association between the specific activities of the respiratory chain complexes and the seminogram parameters and here we have studied the relationship between the spermatozoa OXPHOS activities and L‐carnitine concentration in the seminal plasma. Carnitine, but not prostatic secretions, positive and significantly correlate with mitochondrial respiratory complex activities and the citric acid cycle enzymes citrate synthase and succinate dehydrogenase. It is remarkable that the ratios of the respiratory chain complexes to citrate synthase or succinate dehydrogenase, significant but negatively correlated with L‐carnitine concentration. As carnitine in seminal plasma is secreted from the epididymis our results strongly suggest that relationships between carnitine secretion, seminal quality and OXPHOS activities could be because of a parallel response to the same regulatory event.
The influence of objective measurement tools on communication and clinical decision making in neurological rehabilitation
Authors: Tyson Sarah F. , Greenhalgh Joanne , Long Andrew F. , Flynn Robert
Published: September 2010

Rationale  Routine collection of outcome measures is advocated to improve quality of care. However, there has been scant investigation of how measurement tools are used in clinical practice and what impact they may have. This paper compares two neuro‐rehabilitation teams, one which routinely used standardized measurement tools and the other which did not. We explore differences in communication and clinical decision making within multidisciplinary team (MDT) meetings to illuminate the influence measurement tools could have on clinical practice.

Method  Non‐participant observation of MDT meetings in two neurological rehabilitation units in England. Semi‐structured interviews were also carried out with at least one member of each profession in each team. Grounded theory techniques were used to analyse the data.

Results  Differences in team members' communication within MDT meetings underscored differences in the process of clinical decision making within the teams. Using measurement tools provided a shared understanding to facilitate communication by focusing discussion on the patient's abilities rather than individual professionals' contributions. This led to differences in the way team members identified the nature and cause of patients' problems, monitored their progress and planned for discharge. They provided a ‘neutral ground’ to reach a shared perspective between professionals, thereby avoiding conflict. Externally, use of the tools enabled objective discussion with patients and their families about their progress and was a vehicle to facilitate giving bad news.

Conclusion  Using standardized measurement tools can promote a patient‐focused approach to care, thus facilitating treatment planning and clinical decision making.
Thickness estimation of fluorescent sections using a CSLM
Authors: BRISMAR H. , PATWARDHAN A. , JAREMKO G. , NYENGAARD J.
Published: September 2010

A novel method for the measurement of the section thickness of LM‐plastic embedded specimen has been developed. This method makes use of the fluorescence that comes from standard routine stainings such as haematoxylin and eosin and periodic acid‐Schiff. An x‐z profile of the specimen is first scanned using a confocal scanning laser microscope. The full‐width half‐maximum, FWHM, of the profile is computed and used as a measure of the specimen thickness. This method has proven to be simple and quick: a slide with five sections takes less than 1 min to measure. A theoretical treatment is presented which shows that the FWHM of the axial fluorescent profile is a good estimate of the actual thickness when the sample thickness is greater than 20 (when thickness is expressed in generalized longitudinal optical coordinates). This corresponds to a thickness of about 1μm when using an NA=1.3 oil‐immersion objective and 488‐nm excitation. The relative error in thickness is then less than 10%. Simulations and experiments have been carried out to examine how problems such as bleaching, sample tilt and curvature of field influence the FWHM. The results show that the method is robust and insensitive to such problems.
Optical near fields as photon‐matter interacting systems
Authors: Sangu S. , Kobayashi K. , Ohtsu M.
Published: September 2010

A quantum theoretical formulation of an optical near‐field system developed using the projection operator method is shown to be applicable to conventional problems in the optical near field in a unified way, and also addresses different quantum mechanical issues such as atom manipulation and nano‐fabrication. To gain a clear insight, the effective mass of exciton‐polaritons is introduced; this depends on the sizes of the probe tip and sample. We calculate the optical near‐field intensity detected by (a) a probe sphere and (b) tapered probe modelled by two spheres. The results show that the size of the probe tip determines the spatial resolution, while the contribution of the tapered part causes degradation of the signal contrast. A size–resonance effect between the probe and sample is predicted. Furthermore, enhancement of the signal intensity is observed at the edges of a circular aperture perpendicular to incident polarization. These results are consistent with those obtained from different methods. The approach employed is shown to be a valuable tool in physical understanding and analysis of the near‐field optical phenomena as well as experimental situations.
Population structure of an endemic vulnerable species, the Jamaican boa (Epicrates subflavus)
Authors: TZIKA ATHANASIA C. , KOENIG SUSAN , MILLER RICARDO , GARCIA GERARDO , REMY CHRISTOPHE , MILINKOVITCH MICHEL C.
Published: September 2010

The Jamaican boa (Epicrates subflavus; also called Yellow boa) is an endemic species whose natural populations greatly and constantly declined since the late 19th century, mainly because of predation by introduced species, human persecution, and habitat destruction. In‐situ conservation of the Jamaican boa is seriously hindered by the lack of information on demographic and ecological parameters as well as by a poor understanding of the population structure and species distribution in the wild. Here, using nine nuclear microsatellite loci and a fragment of the mitochondrial cytochrome b gene from 87 wild‐born individuals, we present the first molecular genetic analyses focusing on the diversity and structure of the natural populations of the Jamaican boa. A model‐based clustering analysis of multilocus microsatellite genotypes identifies three groups that are also significantly differentiated on the basis of F‐statistics. Similarly, haplotypic network reconstruction methods applied on the cytochrome b haplotypes isolated here identify two well‐differentiated haplogroups separated by four to six fixed mutations. Bayesian and metaGA analyses of the mitochondrial data set combined with sequences from other Boidae species indicate that rooting of the haplotypic network occurs most likely between the two defined haplogroups. Both analyses (based on nuclear and mitochondrial markers) underline an Eastern vs. (Western + Central) pattern of differentiation in agreement with geological data and patterns of differentiation uncovered in other vertebrate and invertebrate Jamaican species. Our results provide important insights for improving management of ex‐situ captive populations and for guiding the development of proper in‐situ species survival and habitat management plans for this spectacular, yet poorly known and vulnerable, snake.
Comparative phylogeography and demographic history of the wood lemming (Myopus schisticolor): implications for late Quaternary history of the taiga species in Eurasia
Authors: FEDOROV V. B. , GOROPASHNAYA A. V. , BOESKOROV G. G. , COOK J. A.
Published: September 2010

The association between demographic history, genealogy and geographical distribution of mitochondrial DNA cytochromebhaplotypes was studied in the wood lemming (Myopus schisticolor), a species that is closely associated with the boreal forest of the Eurasian taiga zone from Scandinavia to the Pacific coast. Except for a major phylogeographic discontinuity (0.9% nucleotide divergence) in southeastern Siberia, only shallow regional genetic structure was detected across northern Eurasia. Genetic signs of demographic expansions imply that successive range contractions and expansions on different spatial scales represented the primary historical events that shaped geographical patterns of genetic variation. Comparison of phylogeographic structure across a taxonomically diverse array of other species that are ecologically associated with the taiga forest revealed similar patterns and identified two general aspects. First, the major south–north phylogeographic discontinuity observed in five out of six species studied in southeastern Siberia and the Far East implies vicariant separation in two different refugial areas. The limited distribution range of the southeastern lineages provides no evidence of the importance of the putative southeastern refugial area for postglacial colonization of northern Eurasia by boreal forest species. Second, the lack of phylogeographic structure associated with significant reciprocal monophyly and genetic signatures of demographic expansion in all nine boreal forest animal species studied to date across most of northern Eurasia imply contraction of each species to a single refugial area during the late Pleistocene followed by range expansion on a continental scale. Similar phylogeographic patterns observed in this taxonomically diverse set of organisms with different life histories and dispersal potentials reflect the historical dynamics of their shared environment, the taiga forest in northern Eurasia.
Independent origins of self‐compatibility in Arabidopsis thaliana
Authors: SHIMIZU KENTARO K. , SHIMIZU‐INATSUGI RIE , TSUCHIMATSU TAKASHI , PURUGGANAN MICHAEL D.
Published: September 2010

The evolution from outcrossing based on self‐incompatibility (SI) to a selfing system is one of the most prevalent transitions in flowering plants. It has been suggested that the loss of SI in Arabidopsis thaliana is associated with pseudogene formation at the SCR male component of the S locus. Recent work, however, suggests that alternative alleles with large deletions at the S locus are also present and may be responsible for the evolution of self‐compatibility in this species. We demonstrate that most of these deletion alleles are evolutionarily derived from an S haplotype (haplogroups A) that already possessed the SCR pseudogene. This haplotype and its deletion variants are nearly fixed in Europe. Together with previous transgenic data, these results suggest that the pseudogenization of ΨSCR1 gene changed the SI phenotype in the majority of A. thaliana accessions, and was a critical step in the evolution of selfing in this species. Two other haplogroups (B and C) were also identified, the former of which contains a novel and possibly functional SCR allele. In contrast to haplogroups A, these two haplogroups are found primarily in Africa and Asia. These results suggest that self‐compatibility, which appears to be fixed in this species, arose multiple times with different genetic bases, and indicates that a species‐specific trait is associated with parallel evolution at the molecular level.
Native range genetic variation in Arabidopsis thaliana is strongly geographically structured and reflects Pleistocene glacial dynamics
Authors: BECK JAMES B. , SCHMUTHS HEIKE , SCHAAL BARBARA A.
Published: September 2010

Despite Arabidopsis thaliana's pre‐eminence as a model organism, major questions remain regarding the geographic structure of its genetic variation due to the geographically incomplete sample set available for previous studies. Many of these questions are addressed here with an analysis of genome‐wide variation at 10 loci in 475 individuals from 167 globally distributed populations, including many from critical but previously un‐sampled regions. Rooted haplotype networks at three loci suggest that A. thaliana arose in the Caucasus region. Identification of large‐scale metapopulations indicates clear east–west genetic structure, both within proposed Pleistocene refugia and post‐Pleistocene colonized regions. The refugia themselves are genetically differentiated from one another and display elevated levels of within‐population genetic diversity relative to recolonized areas. The timing of an inferred demographic expansion coincides with the Eemian interglacial (approximately 120 000 years ago). Taken together, these patterns are strongly suggestive of Pleistocene range dynamics. Spatial autocorrelation analyses indicate that isolation by distance is pervasive at all hierarchical levels, but that it is reduced in portions of Europe.
Replaying the tape: recurring biogeographical patterns in Cape Verde Conus after 12 million years
Authors: CUNHA REGINA L. , TENORIO MANUEL J. , AFONSO CARLOS , CASTILHO RITA , ZARDOYA RAFAEL
Published: September 2010

Isolated oceanic islands are excellent natural laboratories to test the relative role of historical contingency and determinism in evolutionary diversification. Endemics of the marine venomous snail Conus in the Cape Verde archipelago were originated from at least two independent colonizations of ‘small’ and ‘large’ shelled species separated by 12 million years. In this study, we have reconstructed phylogenetic relationships within large‐shelled Conus (C. ateralbus, C. pseudonivifer, C. trochulus, and C. venulatus) based on mitochondrial cox1 and nad4 haplotype sequences. The reconstructed molecular phylogeny revealed three well‐supported and relatively divergent clades (A, B, and C) that do not correspond to current species classification based on shell colour and banding patterns. Clade A grouped specimens assigned either to C. pseudonivifer or C. trochulus, clade B is composed of specimens assigned to C. venulatus, and clade C comprises specimens assigned either to C. venulatus or C. ateralbus. Geometric morphometric analyses found significant differences between the radular teeth shape of C. pseudonivifer/C. trochulus and C. venulatus/C. ateralbus. In clades A and B, northwestern Boavista and Maio specimens cluster together to the exclusion of eastern Boavista samples. In Sal, populations form a monophyletic island assemblage (clade C). The large‐shelled Conus have remarkably replicated biogeographical patterns of diversification of small‐shelled Conus. Similar selective forces (i.e. nonplanktonic lecithotrophy with limited larval dispersal and allopatric diversification) together with repeated instances of low sea level stands during glacial maxima that allowed connection between islands, have overcome the effect of historical contingency, and explain the observed recurring biogeographical patterns.
Colonization history of the Swiss Rhine basin by the bullhead (Cottus gobio): inference under a Bayesian spatially explicit framework
Authors: NEUENSCHWANDER SAMUEL , LARGIADÈR CARLO R. , RAY NICOLAS , CURRAT MATHIAS , VONLANTHEN PASCAL , EXCOFFIER LAURENT
Published: September 2010

The present distribution of freshwater fish in the Alpine region has been strongly affected by colonization events occurring after the last glacial maximum (LGM), some 20 000 years ago. We use here a spatially explicit simulation framework to model and better understand their colonization dynamics in the Swiss Rhine basin. This approach is applied to the European bullhead (Cottus gobio), which is an ideal model organism to study fish past demographic processes since it has not been managed by humans. The molecular diversity of eight sampled populations is simulated and compared to observed data at six microsatellite loci under an approximate Bayesian computation framework to estimate the parameters of the colonization process. Our demographic estimates fit well with current knowledge about the biology of this species, but they suggest that the Swiss Rhine basin was colonized very recently, after the Younger Dryas some 6600 years ago. We discuss the implication of this result, as well as the strengths and limits of the spatially explicit approach coupled to the approximate Bayesian computation framework.
Cross‐linking FtsZ polymers into coherent Z rings
Authors: Dajkovic Alex , Pichoff Sebastien , Lutkenhaus Joe , Wirtz Denis
Published: September 2010

A key event in bacterial cytokinesis is the formation of the Z ring, which serves as a mechanical scaffold that recruits other cytokinetic proteins to establish functional divisomes. This scaffolding function of Z rings is essential throughout cytokinesis, but the underlying molecular interactions are poorly understood. Here we report that a widely conserved FtsZ binding protein, ZapA, has cytological, biochemical and biophysical properties that argue for the importance of cross‐linking interactions between FtsZ polymers in the coherence of Z rings. Escherichia coli zapA null mutant cells have Z rings that are structurally looser and many helical precursors of Z rings fail to coalesce into coherent rings. Biophysical behaviour of FtsZ in the presence of ZapA reveals that ZapA not only bundles, but also cross‐links FtsZ polymers, which makes it the first cross‐linking protein of the bacterial cytoskeleton. Cross‐linking in vitro occurs at the stoichiometry of FtsZ–ZapA interaction at the Z rings in vivo, where nearly all intracellular ZapA is dynamically associated. ZapA also stabilizes longitudinal bonds between FtsZ monomers since it promotes the polymerization of FtsZ mutants with lesions at the polymerization interface and since it reverses the inhibitory effects of SulA, a known antagonist of FtsZ longitudinal interactions.
Facies, cycles, and controls on the evolution of a keep‐up carbonate platform (Kimmeridgian, Swiss Jura)
Authors: COLOMBIÉ CLAUDE , STRASSER ANDRE
Published: September 2010

During the Late Jurassic, accelerated ocean‐floor spreading and associated sea‐level rise were responsible for a worldwide transgression, which reached its maximum in the Late Kimmeridgian. In many Western European basins, this major sea‐level rise led to the formation of marly and condensed sections. In the Swiss Jura, however, a shallow carbonate platform kept growing and only subtle changes in the stratigraphic record suggest an increasingly open‐marine influence. Field observations and thin‐section analyses reveal that the central Swiss Jura was at that time occupied by tidal flats and by more or less open marine lagoons where shoals and bioherms developed. The evolution through time of sedimentary facies and bed thicknesses permits the definition of small‐, medium‐, and large‐scale depositional sequences. The diagnostic features of these sequences are independent of scale and seem largely controlled by the Kimmeridgian second‐order transgression. A high‐resolution sequence‐stratigraphic correlation with biostratigraphically well‐dated hemipelagic and pelagic sections in the Vocontian Basin in France reveals that: (i) The most important increase in accommodation recorded in the Kimmeridgian of the central Swiss Jura occurs in the Eudoxus ammonite zone (Late Kimmeridgian) and corresponds to the second‐order maximum flooding recognized in many sedimentary basins. (ii) The small‐ and medium‐scale sequences have time durations corresponding to the first and second orbital eccentricity cycle (i.e. 100 and 400 ka, respectively), suggesting that sedimentation on the platform and in the basin was at least partly controlled by cyclic environmental changes induced by insolation variations in the Milankovitch frequency band. The comparison of the high‐resolution temporal framework defined in the Swiss Jura and Vocontian Basin with the sequence‐stratigraphic interpretation realized in other Western European basins shows that the large‐scale sequence boundaries defined in the Kimmeridgian of the Swiss Jura appear in comparable biostratigraphic positions in most Western European basins. Discrepancies that occur are probably because of local or regional tectonics.
Hindered settling of sand grains
Authors: TOMKINS MATT R. , BALDOCK TOM E. , NIELSEN PETER
Published: September 2010

The sedimentation rate of sand grains in the hindered settling regime has been considered to assess particle shape effects. The behaviour of various particulate systems involving sand has been compared with the widely used Richardson–Zaki expression. The general form of the expression is found to hold, in as much as remaining as a suitable means to describe the hindered settling of irregular particles. The sedimentation exponent n in the Richardson–Zaki expression is found to be significantly larger for natural sand grains than for regular particles. The hindered settling effect is therefore greater, leading to lower concentration gradients than expected. The effect becomes more pronounced with increasing particle irregularity. At concentrations around 0·4, the hindered settling velocity of fine and medium natural sands reduces to about 70% of the value predicted using existing empirical expressions for n. Using appropriate expressions for the fluidization velocity and the clear water settling velocity, a simple method is discussed to evaluate the sedimentation exponent and to determine the hindered settling effect for sands of various shapes.
Giant calcite‐cemented concretions, Dakota Formation, central Kansas, USA
Authors: MCBRIDE EARLE F. , MILLIKEN KITTY L.
Published: September 2010

Giant spheroidal concretions (cannonball concretions; some nearly 6 m in diameter) in fluvial channel‐fill sandstones at two localities of the Dakota Sandstone formed by import of cement constituents at a burial depth of <1 km. During cannonball concretion growth a self‐organizational process restricted concretions to a relatively few but widely spaced, and locally, evenly spaced, sites. Other forms of calcite cements at these localities are cement patches in the form of intergrown grape‐size concretions (grapestone), and, locally, pervasive cement. An early episode of invasion by thermogenically generated H2S, which reacted with iron oxides on detrital grains, generated scattered pyrite crystals and decimetre‐scale spheroidal pyrite concretions. Intergranular volumes (IGV) in the concretions range from 36% to 27%. The absence of a trend in IGV and of carbon and oxygen‐isotope ratios from cannonball centres to margins indicates that these concretions did not cement progressively outwards from the centre. Rather, the modern spheres represent the spatial extent of nucleation sites that were not otherwise organized within that volume. Carbon and oxygen‐isotope values for concretion calcites plot along a swath between depleted values of δ18C of −36‰ and δ18O of −13‰ and enriched values of −4‰ and −6‰, respectively. Four groups of calcites are evident on the basis of trace‐element content and suggest that the calcite precipitated across a range of oxidation conditions that do not correlate strongly with the isotopic compositions. Although fluvial overbank sandstones have some pedogenic calcite, the channel sandstones have at most a trace of pedogenic calcite and carbonate rock fragments, so that the bulk of cement components were imported to the sandstones. Carbon and calcium sources for calcite cement include marine limestone, carbonate shells, and anhydrite in addition to HCO derived from oxidized methane, most likely derived from beds underlying or laterally in communication with Dakota sandstones. HCO in ascending formation waters, released during compaction, mixed with meteoric water whose temperature and composition varied with time, to generate the 7‰ range in δ18Ocalcite values measured.
Light‐activation of NADP‐malate dehydrogenase: A highly controlled process for an optimized function
Authors: Miginiac‐Maslow M. , Johansson K. , Ruelland E. , Issakidis‐Bourguet E. , Schepens I. , Goyer A. , Lemaire‐Chamley M. , Jacquot J.‐P. , Le Maréchal P. , Decottignies P.
Published: September 2010

The chloroplastic nicotinamide adenine dinucleotide phosphate‐malate dehydrogenase (NADP‐MDH) (EC 1.1.1.82), a key enzyme of photosynthetic carbon assimilation of the C4 NADP‐malic enzyme type plants, is strictly regulated by light through the ferredoxin‐thioredoxin system. It is inactive in the dark, in the oxidized form, and activated in the light by the reduction of specific regulatory disulfides. A site‐directed mutagenesis approach allowed localization of the regulatory disulfides in the N‐ and C‐terminal sequence extensions conserved in all the light‐regulated chloroplastic malate dehydrogenases. These extensions do not exist in the permanently active NAD‐dependent MDHs (EC 1.1.1.37). Biochemical characterization of the mutants and elimination of negative charges at the C‐terminus provided evidence for auto‐inhibition of the oxidized enzyme by its C‐terminal end through interaction with the active site and showed that the more compact structure of the oxidized dimer was linked to the presence of the N‐terminal disulfide. The recently published 3‐dimensional structures of the oxidized enzyme confirmed the location of the regulatory disulfides and fully support the auto‐inhibition hypothesis. Indeed, the C‐terminus is trapped inside the active site, interacting with active‐site residues, and the N‐termini are inserted at the dimer contact area where they are bound by hydrophobic interactions with both subunits. The physiological function of such complex regulation is discussed.
Integration of metabolomics and proteomics in molecular plant physiology – coping with the complexity by data‐dimensionality reduction
Authors: Weckwerth Wolfram
Published: September 2010

In recent years, genomics has been extended to functional genomics. Toward the characterization of organisms or species on the genome level, changes on the metabolite and protein level have been shown to be essential to assign functions to genes and to describe the dynamic molecular phenotype. Gas chromatography (GC) and liquid chromatography coupled to mass spectrometry (GC‐ and LC‐MS) are well suited for the fast and comprehensive analysis of ultracomplex metabolite samples. For the integration of metabolite profiles with quantitative protein profiles, a high throughput (HTP) shotgun proteomics approach using LC‐MS and label‐free quantification of unique proteins in a complex protein digest is described. Multivariate statistics are applied to examine sample pattern recognition based on data‐dimensionality reduction and biomarker identification in plant systems biology. The integration of the data reveal multiple correlative biomarkers providing evidence for an increase of information in such holistic approaches. With computational simulation of metabolic networks and experimental measurements, it can be shown that biochemical regulation is reflected by metabolite network dynamics measured in a metabolomics approach. Examples in molecular plant physiology are presented to substantiate the integrative approach.
Convulsive effects of thiophene, a heterocyclic hydrocarbon: Behavioral, electrographic and c‐Fos immunocytochemical studies
Authors: Mori Fumiaki , Tanji Kunikazu , Wakabayashi Koichi
Published: September 2010

The behavioral, electrographic and histopathological changes induced by the heterocyclic hydrocarbon thiophene were investigated in rats following intramuscular injection of 0.3 mL thiophene for 5 days. Generalized convulsions were noted in 29 out of 34 animals (85%) between 1 and 28 h after the final dose. Electroencephalography revealed that the discharges in the hippocampus and forebrain occurred simultaneously, although epileptic activity emerged more strongly from the hippocampus than from any other region. Neuron damage was detected histologically in the temporal and parietal neocortex, piriform gyrus, amygdaloid nucleus and cerebellar cortex, but not in the hippocampus. In contrast, c‐Fos was induced widely in the cerebral cortex and hippocampus, and was most marked in the dentate gyrus. These findings suggest that the hippocampus plays a crucial role in seizure onset following thiophene injection.
Immunohistochemical analysis of brainstem lesions in infantile spasms
Authors: Hayashi Masaharu , Itoh Masahiro , Araki Satoshi , Kumada Satoko , Tanuma Naoyuki , Kohji Toshihiko , Kohyama Jun , Iwakawa Yoshihide , Satoh Junichi , Morimatsu Yoshio
Published: September 2010

Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium‐binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox–Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine–enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH‐immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti‐PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients.
Formation of advanced glycation end‐product‐modified superoxide dismutase‐1 (SOD1) is one of the mechanisms responsible for inclusions common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutation, and transgenic mice expressing human SOD1 gene mutation
Authors: Kato Shinsuke , Nakashima Kenji , Horiuchi Seikoh , Nagai Ryoji , Cleveland Don W. , Liu Jian , Hirano Asao , Takikawa Miki , Kato Masako , Nakano Imaharu , Sakoda Saburo , Asayama Kohtaro , Ohama Eisaku
Published: September 2010

Neuronal Lewy body‐like hyaline inclusions (LBHI) and astrocytic hyaline inclusions (Ast‐HI) are morphological hallmarks of certain familial amyotrophic lateral sclerosis (FALS) patients with superoxide dismutase‐1 (SOD1) gene mutations, and transgenic mice expressing the human SOD1 gene mutation. The ultrastructure of inclusions in both diseases is identical: the essential common constituents are granule‐coated fibrils approximately 15– 25 nm in diameter and granular materials. Detailed immunohistochemical analyses have shown that the essential common protein of the inclusions in both diseases is an SOD1 protein. This finding, together with the immunoelectron microscopy finding that the abnormal granule‐coated fibrils comprising the inclusions are positive for SOD1, indicates that these granule‐coated fibrils containing SOD1 are important evidence for mutant SOD1‐linked disease in human and mouse. For im‐munoelectron microscopy, the granule‐coated fibrils are modified by advanced glycation endproducts (AGE) such as Nɛ‐carboxymethyl lysine, pyrraline and pentosidine (Maillard reaction). Based on the fact that AGE themselves are insoluble molecules with direct cytotoxic effects, the granule‐coated fibrils and granular materials are not digested by the lysosomal and ubiquitin systems. The neurons and astrocytes of the normal individuals and non‐transgenic mice show no significant immunoreactivity for AGE. Considered with the mutant‐SOD1 aggregation toxicity, a portion of the SOD1 comprising both types of the inclusion is modified by the AGE, and the formation of the AGE‐modified SOD1 (probably AGE‐modified mutant SOD1) is one of the mechanisms responsible for the aggregation (i.e. granule‐coated fibril formation).
Transgenic mouse model for familial amyotrophic lateral sclerosis with superoxide dismutase‐1 mutation
Authors: Shibata Noriyuki
Published: September 2010

Familial amyotrophic lateral sclerosis (ALS) with mutations in the gene for superoxide dismutase‐1 (SOD1) is clinicopathologically reproduced by transgenic mice expressing mutant forms of SOD1 detectable in familial ALS patients. Motor neuron degeneration associated with SOD1 mutation has been thought to result from a novel neurotoxicity of mutant SOD1, but not from a reduction in activity of this enzyme, based on autosomal dominant transmission of SOD1 mutant familial ALS and its transgenic mouse model, clinical severity of the ALS patients independent to enzyme activity, no ALS‐like disease in SOD1 knockout or wild‐type SOD1‐over‐expressing mice, and clinicopathological severity of mutant SOD1 transgenic mice dependent on transgene copy numbers. Proposed mechanisms of motor neuron de‐generation such as oxidative injury, peroxynitrite toxicity, cytoskeletal disorganization, glutamate excitotoxicity, disrupted calcium homeostasis, SOD1 aggregation, car‐bonyl stress and apoptosis have been discussed. Intracy‐toplasmic vacuoles, indicative of increased oxidative damage to the mitochondria and endoplasmic reticulum, in the neuropil and motor neurons appear in high expressors of mutant SOD1 transgenic mice but not in low expressors of the mice or familial ALS patients, suggesting that overexpression of mutant SOD1 in mice may enhance oxidative stress generation from this enzyme. Thus, transgenic mice carrying small transgene copy numbers of mutant SOD1 would provide a beneficial animal model for SOD1 mutant familial ALS. Such a model would contribute to elucidating the pathomechanism of this disease and establishing new therapeutic agents.
Acute focal demyelinating disease simulating brain tumors: Histopathologic guidelines for an accurate diagnosis
Authors: Sugita Yasuo , Terasaki Mizuhiko , Shigemori Minoru , Sakata Kiyohiko , Morimatsu Minoru
Published: September 2010

The object of the present study was to determine the histopathological guidelines for accurate diagnosis of cases of acute focal demyelinating disease that simulates brain tumors. The surgical pathology of three such cases is assessed. Histopathological keys to the diagnosis of such cases are as follows. First, a pattern of sheets of atypical gemistocytic astrocytes in the white matter that show well‐formed processes and that are adequately distanced from each other argues against a diagnosis of neoplasm. Second, uniform distribution of foamy macrophages aligned along axons, with occasional focal collections surrounding blood vessels and in the absence of any associated coagulative necrosis argues against the presence of a tumor. Third, perivascular chronic inflammatory infiltration, especially a mixture of lymphocytes and macrophages, favors the diagnosis of demyelination plaque. In such cases the lymphocytes will be predominantly T cells. Fourth, pleomorphic astrocytic proliferation with a lack of vascular endothelial proliferation should raise the suspicion that the lesion may not be a brain tumor. These diagnostic keys should be followed when diagnosing cases that are suspected to be demyelination processes rather than brain tumors. The presence of demyelination plaque should then be confirmed by imaging modalities such as staining with myelin‐and axon‐specific stains.
Radical cystectomy for patients with pT4 urothelial carcinoma in a large population‐based study
Authors: Liberman Daniel , Alasker Ahmed , Sun Maxine , Ismail Salima , Lughezzani Giovanni , Jeldres Claudio , Budaus Lars , Thuret Rodolphe , Shariat Shahrokh F. , Widmer Hugues , Perrotte Paul , Graefen Markus , Montorsi Francesco , Karakiewicz Pierre I.
Published: September 2010

Study Type – Therapy (cohort) Level of Evidence 2b

What’s known on the subject? and What does the study add?

Given the natural history of pT4 urothelial carcinoma of the urinary bladder, and the substantially poorer survival of pT4 patients relative to pT3, it may be argued that radical cystectomy is not justified in these patients.

Relying on a large population‐based retrospective analysis, the current study identified two main categories of patients with pT4 urothelial carcinoma of the urinary bladder. The first comprised of patients with pT4b disease, whose disease phenotype was clearly more aggressive than their pT3 counterparts. The second group consisted of patients with pT4a disease, whose disease phenotype was very similar to patients with pT3.

These findings indicate that patients with pT4b disease should be provided with the maximal amount of therapeutic interventions, such as administration of early adjuvant chemotherapy and perhaps early adjuvant radiotherapy.

OBJECTIVE

To examine cancer‐specific mortality (CSM) in patients with pT4N0–3M0 urothelial carcinoma of the urinary bladder (UCUB) and to compare it to patients with pT3N0–3M0, in a population‐based cohort treated with radical cystectomy (RC).

PATIENTS AND METHODS

RCs were performed in 5625 pT3‐T4bN0–3M0 patients with UCUB within 17 Surveillance, Epidemiology and End Results (SEER) registries between 1988 and 2006.

Univariable and multivariable models tested the effect of pT4a vs pT4b vs pT3 stages on CSM.

Covariates consisted of age, gender, race, lymph node status and SEER registries.

All analyses were repeated in 3635 pN0 patients.

RESULTS

Of 5625 patients, 2043 (36.3%) had pT4aN0–3, 248 (4.4%) had pT4bN0–3 and 3334 had pT3N0–3 (59.3%) UCUB.

The 5‐year CSM was 57.6% vs 81.7% vs 53.9% for, respectively, pT4aN0–3 vs pT4bN0–3 vs pT3N0–3 patients (all log‐rank P= 0.008).

In multivariable analyses the rate of CSM was 2.3‐fold higher in pT4b vs pT3 (P < 0.001), 1.1‐fold higher in pT4a vs pT3 (P= 0.002) and 2.0‐fold higher in pT4a vs pT4b patients.

After restriction to pN0 stage, pT4b patients had a 2.3‐fold higher rate of CSM than pT3 patients (P < 0.001) and pT4b patients had a 2.1‐fold higher rate of CSM than pT4a patients (P < 0.001).

The CSM rate was the same for pT4a and pT3 patients (P= 0.1).

CONCLUSIONS

Our findings indicate that patients with pT4a UCUB have similar CSM as those with pT3 UCUB.

Consequently, RC should be given equal consideration in patients with pT3 and pT4a UCUB.