bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Cajal Body–specific RNAs ofDrosophilaFunction in the Absence of Cajal Bodies
Authors: Deryusheva Svetlana , Gall Joseph G.
Published: October 2009

During their biogenesis small nuclear RNAs (snRNAs) undergo multiple covalent modifications that require guide RNAs to direct methylase and pseudouridylase enzymes to the appropriate nucleotides. Because of their localization in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific RNAs (scaRNAs). Using a fluorescent primer extension technique, we mapped the modified nucleotides in Drosophila U1, U2, U4, and U5 snRNAs. By fluorescent in situ hybridization (FISH) we showed that seven Drosophila scaRNAs are concentrated in easily detectable CBs. We used two assays based on Xenopus oocyte nuclei to demonstrate that three of these Drosophila scaRNAs do, in fact, function as guide RNAs. In flies null for the CB marker protein coilin, CBs are absent and there are no localized FISH signals for the scaRNAs. Nevertheless, biochemical experiments show that scaRNAs are present at normal levels and snRNAs are properly modified. Our experiments demonstrate that several scaRNAs are concentrated as expected in the CBs of wild-type Drosophila, but they function equally well in the nucleoplasm of mutant flies that lack CBs. We propose that the snRNA modification machinery is not limited to CBs, but is dispersed throughout the nucleoplasm of cells in general.
Accurate confidence aware clustering of array CGH tumor profiles
Authors: van Houte Bart P.P. , Heringa Jaap
Published: October 2009

Motivation: Chromosomal aberrations tend to be characteristic for given (sub)types of cancer. Such aberrations can be detected with array comparative genomic hybridization (aCGH). Clustering aCGH tumor profiles aids in identifying chromosomal regions of interest and provides useful diagnostic information on the cancer type. An important issue here is to what extent individual aCGH tumor profiles can be reliably assigned to clusters associated with a given cancer type.

Results: We introduce a novel evolutionary fuzzy clustering (EFC) algorithm, which is able to deal with overlapping clusterings. Our method assesses these overlaps by using cluster membership degrees, which we use here as a confidence measure for individual samples to be assigned to a given tumor type. We first demonstrate the usefulness of our method using a synthetic aCGH dataset and subsequently show that EFC outperforms existing methods on four real datasets of aCGH tumor profiles involving four different cancer types. We also show that in general best performance is obtained using 1− Pearson correlation coefficient as a distance measure and that extra preprocessing steps, such as segmentation and calling, lead to decreased clustering performance.

Availability: The source code of the program is available from http://ibi.vu.nl/programs/efcwww

Contact:  heringa@few.vu.nl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Reporting bias when using real data sets to analyze classification performance
Authors: Yousefi Mohammadmahdi R. , Hua Jianping , Sima Chao , Dougherty Edward R.
Published: October 2009

Motivation: It is commonplace for authors to propose a new classification rule, either the operator construction part or feature selection, and demonstrate its performance on real data sets, which often come from high-dimensional studies, such as from gene-expression microarrays, with small samples. Owing to the variability in feature selection and error estimation, individual reported performances are highly imprecise. Hence, if only the best test results are reported, then these will be biased relative to the overall performance of the proposed procedure.

Results: This article characterizes reporting bias with several statistics and computes these statistics in a large simulation study using both modeled and real data. The results appear as curves giving the different reporting biases as functions of the number of samples tested when reporting only the best or second best performance. It does this for two classification rules, linear discriminant analysis (LDA) and 3-nearest-neighbor (3NN), and for filter and wrapper feature selection, t-test and sequential forward search. These were chosen on account of their well-studied properties and because they were amenable to the extremely large amount of processing required for the simulations. The results across all the experiments are consistent: there is generally large bias overriding what would be considered a significant performance differential, when reporting the best or second best performing data set. We conclude that there needs to be a database of data sets and that, for those studies depending on real data, results should be reported for all data sets in the database.

Availability: Companion web site at http://gsp.tamu.edu/Publications/supplementary/yousefi09a/

Contact:  edward@ece.tamu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Phagocytic B cells in a reptile
Authors: Zimmerman Laura M. , Vogel Laura A. , Edwards Kevin A. , Bowden Rachel M.
Published: October 2009

Evidence for a developmental relationship between B cells and macrophages has led to the hypothesis that B cells evolved from a phagocytic predecessor. The recent identification of phagocytic IgM+ cells in fishes and amphibians supports this hypothesis, but raises the question of when, evolutionarily, was phagocytic capacity lost in B cells? To address this, leucocytes were isolated from red-eared sliders,Trachemys scripta, incubated with fluorescent beads and analysed using flow cytometry and confocal microscopy. Results indicate that red-eared slider B cells are able to ingest foreign particles and suggest that ectothermic vertebrates may use phagocytic B cells as part of a robust innate immune response.
On the bounding of limit multipliers for combined loading
Authors: Fraldi M. , Nunziante L. , Gesualdo A. , Guarracino F.
Published: October 2009

In the framework of classical plasticity, even when limit multipliers and collapse mechanisms associated with different loads independently acting on a solid or structure are known, not much can be inferred on the limit multiplier of the combined loading. Frame structures under the action of dead loads and seismic forces, soil–foundation interaction problems, tunnels under a variety of loads, deepwater pipelines subject to bending and pressure constitute only a few selected examples for which some sort of superposition rule, as well as bounding techniques, would be extremely useful. The present paper introduces a set of theorems for bounding limit multipliers for combined loads. In particular, ranging from a minimum knowledge about the critical state under a particular loading to a reasonable guess of the kinematics of the problem under combined loads, more and more refined bounds for the overall limit multiplier are derived. The results, to the best of the authors’ knowledge, are novel and a few examples showing their practical value are presented and discussed.
The finite-product method in the theory of waves and stability
Authors: Chapman C. J. , Sorokin S. V.
Published: October 2009

This paper presents a method of analysing the dispersion relation and field shape of any type of wave field for which the dispersion relation is transcendental. The method involves replacing each transcendental term in the dispersion relation by a finite-product polynomial. The finite products chosen must be consistent with the low-frequency, low-wavenumber limit; but the method is nevertheless accurate up to high frequencies and high wavenumbers. Full details of the method are presented for a non-trivial example, that of anti-symmetric elastic waves in a layer; the method gives a sequence of polynomial approximations to the dispersion relation of extraordinary accuracy over an enormous range of frequencies and wavenumbers. It is proved that the method is accurate because certain gamma-function expressions, which occur as ratios of transcendental terms to finite products, largely cancel out, nullifying Runge’s phenomenon. The polynomial approximations, which are unrelated to Taylor series, introduce no spurious branches into the dispersion relation, and are ideal for numerical computation. The method is potentially useful for a very wide range of problems in wave theory and stability theory.
Strong ellipticity and progressive waves in elastic materials with voids
Authors: Chiriţă Stan , Ghiba Ionel-Dumitrel
Published: October 2009

In the present paper, we investigate a model for propagating progressive waves associated with the voids within the framework of a linear theory of porous media. Owing to the use of lighter materials in modern buildings and noise concerns in the environment, such models for progressive waves are of much interest to the building industry. The analysis of such waves is also of interest in acoustic microscopy where the identification of material defects is of paramount importance to the industry and medicine. Our analysis is based on the strong ellipticity of the poroelastic materials. We illustrate the model of progressive wave propagation for isotropic and transversely isotropic porous materials. We also study the propagation of harmonic plane waves in porous materials including the thermal effect.
On the critical equilibrium of the spiral spring pendulum
Authors: Coullet P. , Gilli J.-M. , Rousseaux G.
Published: October 2009

Physical systems such as an inverted pendulum driven by a spiral spring, an unbalanced Euler elastica with a travelling mass, a heavy body with a parabolic section and an Ising ferromagnet are very different. However, they all behave in the same manner close to the critical regime for which nonlinearities are prominent. We demonstrate experimentally, for the first time, an old prediction by Joseph Larmor, which states that a nonlinear oscillator close to its supercritical bifurcation oscillates with a period inversely proportional to its angular amplitude. We perform our experiments with a Holweck–Lejay-like pendulum which was used to measure the gravity field during the twentieth century.
Nanostructured bainite
Authors: Bhadeshia H. K. D. H.
Published: October 2009

An alloy system based on iron is described in which it has been possible to create a high density of interfaces by heat treatment alone. The resulting structure consists of a mixture of slender platelets of bainitic ferrite, just 20–40 nm in thickness, embedded in a matrix of carbon-enriched austenite. The rate at which this structure evolves is slow by conventional standards, but this permits components to be made which are large in all three dimensions, with uniform properties throughout. The fundamental mechanisms behind this novel nanostructured steel are reviewed, along with the factors determining its strength, ductility and fracture toughness. It is argued that, although reasonable toughness can be achieved in the context of strength levels exceeding 2000 MPa, the impact toughness remains poor and that it may not be possible to improve this particular parameter.
Helping effort increases with relatedness in bell miners, but ‘unrelated’ helpers of both sexes still provide substantial care
Authors: Wright Jonathan , McDonald Paul G. , te Marvelde Luc , Kazem Anahita J. N. , Bishop Charles M.
Published: October 2009

Indirect fitness benefits from kin selection can explain why non-breeding individuals help raise the young of relatives. However, the evolution of helping by non-relatives requires direct fitness benefits, for example via group augmentation. Here, we examine nest visit rates, load sizes and prey types delivered by breeding pairs and their helpers in the cooperatively breeding bell miner (
Manorina melanophrys
). In this system, males remain in their natal colony while young females typically disperse, and helpers of both sexes often assist at multiple nests concurrently. We found extremely clear evidence for the expected effect of genetic relatedness on individual helping effort per nest within colonies. This positive incremental effect of kinship was facultative—i.e. largely the result of within-individual variation in helping effort. Surprisingly, no sex differences were detectable in any aspect of helping, and even non-relatives provided substantial aid. Helpers and breeders of both sexes regulated their provisioning effort by responding visit-by-visit to changes in nestling begging. Helping behaviour in bell miners therefore appears consistent with adaptive cooperative investment in the brood, and kin-selected care by relatives. Similar investment by ‘unrelated’ helpers of both sexes argues against direct fitness benefits, but is perhaps explained by kin selection at the colony level.
Lower limits of ornithischian dinosaur body size inferred from a new Upper Jurassic heterodontosaurid from North America
Authors: Butler Richard J. , Galton Peter M. , Porro Laura B. , Chiappe Luis M. , Henderson Donald M. , Erickson Gregory M.
Published: October 2009

The extremes of dinosaur body size have long fascinated scientists. The smallest (<1 m length) known dinosaurs are carnivorous saurischian theropods, and similarly diminutive herbivorous or omnivorous ornithischians (the other major group of dinosaurs) are unknown. We report a new ornithischian dinosaur,
Fruitadens haagarorum
, from the Late Jurassic of western North America that rivals the smallest theropods in size. The largest specimens of
Fruitadens
represent young adults in their fifth year of development and are estimated at just 65–75 cm in total body length and 0.5–0.75 kg body mass. They are thus the smallest known ornithischians.
Fruitadens
is a late-surviving member of the basal dinosaur clade Heterodontosauridae, and is the first member of this clade to be described from North America. The craniodental anatomy and diminutive body size of
Fruitadens
suggest that this taxon was an ecological generalist with an omnivorous diet, thus providing new insights into morphological and palaeoecological diversity within Dinosauria. Late-surviving (Late Jurassic and Early Cretaceous) heterodontosaurids are smaller and less ecologically specialized than Early (Late Triassic and Early Jurassic) heterodontosaurids, and this ecological generalization may account in part for the remarkable 100-million-year-long longevity of the clade.
Theta bursts in the olfactory nerve paired with β-adrenoceptor activation induce calcium elevation in mitral cells: A mechanism for odor preference learning in the neonate rat
Authors: Yuan Qi
Published: October 2009

Odor preference learning in the neonate rat follows pairing of odor input and noradrenergic activation of β-adrenoceptors. Odor learning is hypothesized to be supported by enhanced mitral cell activation. Here a mechanism for enhanced mitral cell signaling is described. Theta bursts in the olfactory nerve (ON) produce long-term potentiation (LTP) of glomerular excitatory postsynaptic potentials (EPSPs) and of excitatory postsynaptic currents (EPSCs) in the periglomerular (PG) and external tufted (ET) cells. Theta bursts paired with β-adrenoceptor activation significantly elevate mitral cell (MC) calcium. Juxtaglomerular inhibitory network depression by β-adrenoceptor activation appears to increase calcium in MCs in response to theta burst stimulation.
Arabidopsis FAB1/PIKfyve Proteins Are Essential for Development of Viable Pollen
Authors: Whitley Paul , Hinz Steven , Doughty James
Published: October 2009

Phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P  2] is a phospholipid that has a role in controlling membrane trafficking events in yeast and animal cells. The function of this lipid in plants is unknown, although its synthesis has been shown to be up-regulated upon osmotic stress in plant cells. PtdIns(3,5)P  2 is synthesized by the PIKfyve/Fab1 family of proteins, with two orthologs, FAB1A and FAB1B, being present in Arabidopsis (Arabidopsis thaliana). In this study, we attempt to address the role of this lipid by analyzing the phenotypes of plants mutated in FAB1A and FAB1B. It was not possible to generate plants homozygous for mutations in both genes, although single mutants were isolated. Both homozygous single mutant plant lines exhibited a leaf curl phenotype that was more marked in FAB1B mutants. Genetic transmission analysis revealed that failure to generate double mutant lines was entirely due to inviability of pollen carrying mutant alleles of both FAB1A and FAB1B. This pollen displayed severe defects in vacuolar reorganization following the first mitotic division of development. The presence of abnormally large vacuoles in pollen at the tricellular stage resulted in the collapse of the majority of grains carrying both mutant alleles. This demonstrates a crucial role for PtdIns(3,5)P  2 in modulating the dynamics of vacuolar rearrangement essential for successful pollen development. Taken together, our results are consistent with PtdIns(3,5)P  2 production being central to cellular responses to changes in osmotic conditions.
Petunia hybrida
CAROTENOID CLEAVAGE DIOXYGENASE7 Is Involved in the Production of Negative and Positive Branching Signals in Petunia
Authors: Drummond Revel S.M. , Martínez-Sánchez N. Marcela , Janssen Bart J. , Templeton Kerry R. , Simons Joanne L. , Quinn Brian D. , Karunairetnam Sakuntala , Snowden Kimberley C.
Published: October 2009

One of the key factors that defines plant form is the regulation of when and where branches develop. The diversity of form observed in nature results, in part, from variation in the regulation of branching between species. Two CAROTENOID CLEAVAGE DIOXYGENASE (CCD) genes, CCD7 and CCD8, are required for the production of a branch-suppressing plant hormone. Here, we report that the decreased apical dominance3 (dad3) mutant of petunia (Petunia hybrida) results from the mutation of the PhCCD7 gene and has a less severe branching phenotype than mutation of PhCCD8 (dad1). An analysis of the expression of this gene in wild-type, mutant, and grafted petunia suggests that in petunia, CCD7 and CCD8 are coordinately regulated. In contrast to observations in Arabidopsis (Arabidopsis thaliana), ccd7ccd8 double mutants in petunia show an additive phenotype. An analysis using dad3 or dad1 mutant scions grafted to wild-type rootstocks showed that when these plants produce adventitious mutant roots, branching is increased above that seen in plants where the mutant roots are removed. The results presented here indicate that mutation of either CCD7 or CCD8 in petunia results in both the loss of an inhibitor of branching and an increase in a promoter of branching.
Mature acinar cells are refractory to carcinoma development by targeted activation of Ras oncogene in adult rats
Authors: Tanaka Hajime , Fukamachi Katsumi , Futakuchi Mitsuru , Alexander David B. , Long Ne , Tamamushi Shojiro , Minami Kohtaro , Seino Susumu , Ohara Hirotaka , Joh Takashi , Tsuda Hiroyuki
Published: October 2009

Pancreatic ductal adenocarcinoma (PDA) is one of the most debilitating malignancies in humans. A thorough understanding of the cytogenesis of this disease will aid in establishing successful treatments. We have developed an animal model which uses adult HrasG12V and KrasG12V transgenic rats in which oncogene expression is regulated by the Cre/loxP system and neoplastic lesions are induced by injection of adenovirus‐expressing Cre recombinase. When adenovirus with Cre recombinase under the control of the CMV enhancer/chicken β‐actin (CAG) promoter (Ad‐CAG‐Cre) is injected into the pancreatic duct of these animals, pancreatic neoplasias develop. Pathologically, the origin of these lesions is duct, intercalated duct, and centroacinar cells, but not acinar cells. The present study was undertaken to test the effect of acinar cell‐specific oncogenic ras expression. Adult transgenic rats were injected with adenovirus with Cre recombinase under the control of the acinar cell‐specific promoters amylase (Ad‐Amy‐Cre) and elastase‐1 (Ad‐Ela‐Cre) or under the control of the non‐specific CAG promoter. Injection of either Ad‐Amy‐Cre or Ad‐Ela‐Cre into the pancreatic ducts of transgenic animals in which oncogenic Kras is tagged with hemagglutinin (HA), HA‐KrasG12V rats resulted in expression of oncogenic ras in acinar cells but not in duct, intercalated duct, or centroacinar cells. Notably, injected animals did not develop any observable proliferative or neoplastic lesions. In marked contrast, injection of Ad‐CAG‐Cre resulted in pancreatic cancer development within 4 weeks. These results indicate that adult acinar cells are refractory to Ras oncogene activation and do not develop neoplasia in this model. (Cancer Sci2009)
Evolution of prognostic factors in hepatocellular carcinoma in Japan
Authors: NOUSO K. , KOBAYASHI Y. , NAKAMURA S. , KOBAYASHI S. , TOSHIMORI J. , KUWAKI K. , HAGIHARA H. , ONISHI H. , MIYAKE Y. , IKEDA F. , SHIRAHA H. , TAKAKI A. , IWASAKI Y. , KOBASHI H. , YAMAMOTO K.
Published: October 2009

Aliment Pharmacol Ther 31, 407–414

Background  The surveillance of hepatocellular carcinoma (HCC) has become prevalent, and the modalities for its treatment have improved.

Aim  To understand the changes that occur in the characteristics and prognostic factors of HCC with time.

Methods  Newly diagnosed HCC patients were divided into two groups; patients treated before 31 December 2000 (n = 504), and after 1 January 2001 (n = 746), and their clinical backgrounds and prognostic factors were analysed.

Results  The number of patients negative for both Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibody (HCVAb) increased with time (NBNC‐HCC). The size of HCC decreased in patients who were positive for HBsAg (B‐HCC) or HCVAb (C‐HCC), whereas no difference was observed in NBNC‐HCC. The patient survival of C‐HCC improved; however, no difference was detected for NBNC‐HCC. In multivariate analysis, low albumin, high aspartate aminotransferase (AST), ascites, large tumour size, multiple tumour number and high alpha‐fetoprotein were risk factors for survival before 2000, whereas the presence of HBsAg was additionally selected as a good prognostic factor and AST was excluded after 2001.

Conclusions  The prognostic factors as well as clinical background of HCC changed with time, and the presence of HBsAg was found to be an additional good prognostic factor after 2001.
Profound hypocalcaemia in a patient being anticoagulated with citrate for continuous renal replacement therapy
Authors: Morgan D. J. R. , Ho K. M.
Published: October 2009

Citrate, as an anticoagulant for continuous renal replacement therapy in critically ill patients, has some potential advantages over heparin, including a prolonged dialysis filter life and reduced risk of bleeding. The key parameter involved in monitoring the adequacy and safety of citrate anticoagulation during continuous renal replacement therapy pertains to the ionised and total plasma calcium levels. We report a case of severe systemic hypocalcaemia during continuous renal replacement therapy with citrate anticoagulation resulting from relentless sequestration of calcium due to undiagnosed evolving rhabdomyolysis. Although excessive systemic citrate accumulation can also cause hypocalcaemia, this complication was not observed in our patient. While an acceptable lower limit of ionised calcium remains unknown, severe rhabdomyolysis needs to be considered when a patient’s ionised calcium levels are not responsive to standard calcium replacement therapy during continuous renal replacement therapy using citrate anticoagulation in critically ill patients.
Dental implant removal to facilitate suspension laryngoscopy and laser treatment of an obstructed airway
Authors: Hume‐Smith H. , Fowler A. , Vaz F. , Suaris P.
Published: October 2009

A 29‐year‐old patient presented with dysphonia, dysphagia and a progressive history of stridor over 6 weeks. His past medical history included childhood nasolabial rhabdomyosarcoma treated by surgery, chemotherapy and radiotherapy. This had resulted in marked abnormalities of the facial skeleton, limited neck extension and restricted mouth opening of 1 cm, in part due to dental implants. After careful discussion and planning within a multidisciplinary team, the airway was optimised by temporary removal of the dental implants. This enabled a suspension laryngoscope to be passed, permitting carbon dioxide laser treatment to an obstruction at the laryngeal inlet and eliminating the need for a tracheostomy.
A comparison of the laryngeal mask airway with the facemask and oropharyngeal airway for manual ventilation by first responders in children
Authors: Blevin A. E. , McDouall S. F. , Rechner J. A. , Saunders T. A. , Barber V. S. , Young J. D. , Mason D. G.
Published: October 2009

In adults, first responders to a cardiopulmonary arrest provide better ventilation using a laryngeal mask airway than a facemask. It is unclear if the same is true in children. We investigated this by comparing the ability of 36 paediatric ward nurses to ventilate the lungs of 99 anaesthetised children (a model for cardiopulmonary arrest) using a laryngeal mask airway and using a facemask with an oropharyngeal airway. Anteroposterior chest wall displacement was measured using an ultrasonic detector. Nurses achieved successful ventilation in 74 (75%) of cases with the laryngeal mask airway and 76 (77%) with facemask and oropharyngeal airway (p = 0.89). Median (IQR [range]) time to first breath was longer for the laryngeal mask airway (48 (39–65 [8–149])) s than the facemask/airway (35 (25–53 [14–120]) s; p < 0.0001). In 10 cases (10%) the lungs were ventilated using the laryngeal mask airway but not using the facemask/oropharyngeal airway. We conclude that ventilation is achieved rapidly using a facemask and oropharyngeal airway, and that the laryngeal mask airway may represent a useful second line option for first responders.
The effect of in vivo growth hormone treatment on blood gene expression in adults with growth hormone deficiency reveals potential biomarkers to monitor growth hormone therapy
Authors: Fernández‐Pérez L. , Nóvoa J. , Ståhlberg N. , Santana‐Farré R. , Boronat M. , Marrero D. , Henríquez‐Hernández L. , Norstedt G. , Flores‐Morales A.
Published: October 2009

Objective  Growth hormone (GH) replacement therapy is presently utilized in the treatment of adult GH deficiency (AGHD). Adult responses to GH treatment are highly variable and, apart from measurement of IGF‐I, few tools are currently available for monitoring GH treatment progress. As GH receptors are expressed in certain blood cell types, changes in gene expression in peripheral blood can reflect perturbations induced as a result of GH therapy.

Design/patients  We have carried out a pilot study to identify GH‐responsive genes in blood, and have assessed the utility of GH‐responsive genes in monitoring GH therapy in AGHD. Blood was collected from ten women diagnosed with AGHD syndrome both before and 4 weeks after initiation of GH substitutive therapy. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and changes in response to GH were detected using microarray‐based gene analysis.

Results  All patients responded to GH replacement therapy, with serum levels of IGF‐I increasing by an average of 307% (P = 0·0003) while IGFBP‐3 increased by an average of 182% (P = 0·0002). Serum levels of triglycerides, LDL‐C, HDL‐C, APOA1 or APOB did not change after 1 month of GH treatment. By contrast, we detected an increase in Lp(a) serum levels (P = 0·0149). Using a stringent selection cutoff of P ≤ 0·05, paired analysis identified a set of transcripts that correlated with GH administration. We applied the multivariate statistical technique PLS‐DA to the changes in gene expression, demonstrating their utility in differentiating untreated patients and those undergoing GH replacement therapy.

Conclusion  This study shows that GH‐dependent effects on gene expression in PBMCs can be detected by microarray‐based gene analysis, and our results establish a foundation for the further exploration of peripheral blood as a surrogate to detect exposure to GH therapy.
Ecological consequences of intraspecific variation in lake Daphnia
Authors: DUFFY MEGHAN A.
Published: October 2009

1. Although populations harbour considerable diversity, most ecological studies still assume they are homogeneous. However, mounting evidence suggests that intraspecific diversity is not only common, but also important for interactions with community members. Here, intraspecific variation in Daphnia dentifera in haemoglobin content is shown to be a marker of hypolimnion use.

2. Hypolimnion use differed substantially within and among D. dentifera populations. Daphnia dentifera with haemoglobin resided primarily in the hypolimnion, while D. dentifera lacking haemoglobin migrated vertically. These ‘deep’ and ‘migratory’D. dentifera had different seasonal phenologies and dynamics.

3. Deep and migratory D. dentifera had qualitatively different relationships with an important competitor, Daphnia pulicaria. Deep D. dentifera density was negatively correlated with D. pulicaria density, whereas migratory density was not correlated with D. pulicaria density.

4. Given that D. pulicaria tends to reside in the hypolimnion, this negative correlation probably reflects competition between D. pulicaria and the deep D. dentifera. This pattern would have been missed if only the relationship between the overall lake populations of D. dentifera and D. pulicaria had been studied.

5. Abundances of deep D. dentifera and D. pulicaria were both correlated with the size of the hypolimnetic refuge from fish predation, but in opposite directions. Lakes with large refuges generally had high D. pulicaria and low deep D. dentifera densities.
Mammalian COP9 signalosome
Authors: Kato Jun‐ya , Yoneda‐Kato Noriko
Published: October 2009

The COP9 signalosome (CSN) complex is highly conserved from yeast to human. Although the plant CSN was first identified as a negative regulator of photomorphogenesis, the mammalian CSN is linked to different biological responses such as checkpoint control, signal transduction, development and the cell cycle. Frequent over‐expression of the CSN subunit in a variety of human cancers suggests its involvement in cell transformation and tumorigenesis. The best‐known biochemical function associated with the CSN is the control of protein stability via the ubiquitin–proteasome system through regulation of cullin‐RING‐E3 ubiquitin ligase activity by deneddylation, by controlling the activity of COP1 E3 ligase, or by counteracting ubiquitin‐mediated degradation through a CSN‐associated deubiquitinating enzyme. In addition to affecting the stability of transcription factors, the CSN may regulate gene transcription by directly associating with chromatin. This review summarizes recent findings and discusses the physiological role and the cellular function of the mammalian CSN in terms of the regulation of cell proliferation.
Rising concentrations of atmospheric CO2 have increased growth in natural stands of quaking aspen (Populus tremuloides)
Authors: COLE CHRISTOPHER T. , ANDERSON JON E. , LINDROTH RICHARD L. , WALLER DONALD M.
Published: October 2009

As atmospheric CO2 levels rise, temperate and boreal forests in the Northern Hemisphere are gaining importance as carbon sinks. Quantification of that role, however, has been difficult due to the confounding effects of climate change. Recent large‐scale experiments with quaking aspen (Populus tremuloides), a dominant species in many northern forest ecosystems, indicate that elevated CO2 levels can enhance net primary production. Field studies also reveal that droughts contribute to extensive aspen mortality. To complement this work, we analyzed how the growth of wild aspen clones in Wisconsin has responded to historical shifts in CO2 and climate, accounting for age, genotype (microsatellite heterozygosity), and other factors. Aspen growth has increased an average of 53% over the past five decades, primarily in response to the 19.2% rise in ambient CO2 levels. CO2‐induced growth is particularly enhanced during periods of high moisture availability. The analysis accounts for the highly nonlinear changes in growth rate with age, and is unaffected by sex or location sampled. Growth also increases with individual heterozygosity, but this heterozygote advantage has not changed with rising levels of CO2 or moisture. Thus, increases in future growth predicted from previous large‐scale, common‐garden work are already evident in this abundant and ecologically important tree species. Owing to aspen's role as a foundation species in many North American forest ecosystems, CO2‐stimulated growth is likely to have repercussions for numerous associated species and ecosystem processes.
To circumcise or not to circumcise? Circumcision in patients with bleeding disorders
Authors: RODRIGUEZ V. , TITAPIWATANAKUN R. , MOIR C. , SCHMIDT K. A. , PRUTHI R. K.
Published: October 2009

Summary.  Circumcision is one of the most common procedures performed in male neonates, but few published reports have described circumcision in patients with bleeding disorders. The aim of this study was to analyse outcomes of circumcision among children evaluated at our institution to determine the extent of complications and to provide guidelines for circumcision management. We searched our patient database for records of children who were followed up at the Mayo Clinic Comprehensive Hemophilia Center from 2000 through 2007 and who had been circumcised. We retrospectively reviewed the medical records to document complications and determine management strategies in this patient population. Of 55 children and young adults identified (median [range] age, 15 years [11 months to 21 years]), 48 patients were circumcised. Indications for circumcision were parental request (n = 45) and medical recommendation (n = 3). Twelve of 21 patients with a known bleeding disorder at the time of circumcision received factor replacement before the procedure. Three of these 21 patients had bleeding complications. Of the other 27 patients, who were diagnosed later in life as having a bleeding disorder, 8 had bleeding complications. The overall incidence of bleeding after circumcision was 23% (11/48). The 23% overall incidence of bleeding complications in our patients with bleeding disorders is comparable to that reported for patients without a bleeding disorder (0.1–35%). Some of our patients had significant bleeding despite adequate factor replacement before and after the procedure. Parents and patients must be aware that bleeding risk is a possibility despite adequate factor replacement for hemostasis.
Effect of glycoPEGylation on factor VIIa binding and internalization
Authors: SEN P. , GHOSH S. , EZBAN M. , PENDURTHI U. R. , VIJAYA MOHAN RAO L.
Published: October 2009

Summary.  Recombinant coagulation factor VIIa (rFVIIa), which is widely used for treatment of bleeding episodes in haemophilia patients with inhibitors, is cleared from the circulation relatively fast with a plasma half‐life of 2–4 h. PEGylation is an established and clinically proven strategy for prolonging the circulatory life‐time of bio‐therapeutic proteins. The aim of this study was to investigate the effect of glycoPEGylation of rFVIIa on rFVIIa binding to its cellular receptors and its subsequent internalization. rFVIIa and glycoPEGylated rFVIIa were labeled with 125I and the radio‐iodinated proteins were used to monitor rFVIIa binding and uptake in endothelial cells and fibroblasts. FVIIa‐TF activity at the cell surface was analyzed by a factor X activation assay. Modification of rFVIIa with PEG impaired rFVIIa binding to both endothelial cell protein C receptor and tissue factor (TF) on cell surfaces. The internalization of PEGylated rFVIIa in endothelial cells and fibroblasts was markedly lower compared to the internalization of rFVIIa in these cells. PEGylated rFVIIa was able to activate factor X on TF expressing cell surfaces at a rate similar to that of unmodified rFVIIa when the cells were not subjected to multiple washings to remove the free ligand. General effects such as steric hindrance or changes in electrostatic binding properties of the modified rFVIIa to its receptors are probably responsible for this impairment rather than a loss of specific recognition of the receptors, which could explain near normal activation of factor X by glycoPEGylated rFVIIa on TF expressing cells while its uptake is reduced.
A study of reported factor VIII use around the world
Authors: STONEBRAKER J. S. , BROOKER M. , AMAND R. E. , FARRUGIA A. , SRIVASTAVA A.
Published: October 2009

Summary.  The effect of replacement therapy has significantly improved the morbidity and mortality of people with haemophilia A in high income countries, a recent socio‐economic development as the availability of safe concentrates has been matched by a willingness for their provision through reimbursement. In the developing world, however, this state has not been achieved, primarily because of the low visibility of haemophilia coupled with its expense, leading to inadequate treatment with its sequelae of severe pain, joint deformities, arthropathy, disabilities, and even death in childhood or early adult life. The objective of this paper was to study the reported factor VIII (FVIII) use on a country‐by‐country basis. Data on the reported FVIII use for 104 countries were obtained from the Marketing Research Bureau, Inc. and the World Federation of Hemophilia. The results show that FVIII use varies considerably among countries, even among the wealthiest of countries. The use of FVIII concentrate increases as economic capacity increases; in addition, consumption of FVIII has been increasing at a greater rate in high income countries. Given these trends, there probably will be a global increase in FVIII concentrates usage. Such information is critical for national healthcare agencies to determine realistic budget priorities in planning for an increased allocation of resources required to improve the treatment of patients with haemophilia A. This information is also important for pharmaceutical manufacturers to adequately plan for increased production of FVIII concentrates.
Abundant nuclear copies of mitochondrial origin (NUMTs) in the Aedes aegypti genome
Authors: Black IV W. C. , Bernhardt S. A.
Published: October 2009

A portion of the Aedes aegypti mitochondrial NADH dehydrogenase subunit 4 gene (ND4) was amplified using PCR with a 42 °C annealing temperature. Amplified fragments from individual mosquitoes were similar to ND4 but contained multiple segregating sites. We suspected that nuclear copies of mitochondrial origin (NUMTs) exist in the Ae. aegypti genome. A BlastN search in VectorBase with the entire Ae. aegypti mitochondrial genome identified 233 NUMTs comprising 110 178 bp in 145 supercontigs. At a density of 0.080 bp/kb, this represents the second highest density of NUMTs in an insect genome and the highest in Diptera. Analyses of flanking sequences suggested that Ae. aegypti NUMTs arise through mtDNA leakage from damaged mitochondria followed by breakage and nonhomologous recombination, rather than through duplicative processes such as transposition or molecular drive.
A coleopteran triosephosphate isomerase: X‐ray structure and phylogenetic impact of insect sequences
Authors: Knobeloch D. , Schmidt A. , Scheerer P. , Krauss N. , Wessner H. , Scholz Ch. , Küttner G. , Von Rintelen T. , Wessel A. , Höhne W.
Published: October 2009

A coleopteran triosephosphate isomerase (TIM) from Tenebrio molitor (yellow mealworm beetle) was recombinantly expressed in Escherichia coli and characterized with respect to thermal stability, kinetic parameters and oligomeric state. The enzyme was successfully crystallized and the structure determined by X‐ray analysis to 2.0 Å resolution. This is the first example of an invertebrate TIM. We compare structural features with known structures of TIMs from microorganisms, plants and vertebrates, and discuss the utility of the Tenebrio TIM sequence, together with several newly sequenced insect TIMs, for molecular phylogenetic analysis.
HAADF‐STEM analysis of layered double perovskite La2CuSnO6 grown epitaxially
Authors: HARUTA M. , KOMATSU H. , KURATA H. , SHIMAKAWA Y. , ISODA S.
Published: October 2009

Structural observation of layered double perovskite oxide La2CuSnO6 thin films grown epitaxially on SrTiO3 is reported by high‐angle annular dark‐field scanning transmission electron microscopy (HAADF‐STEM). Particularly the transition layer at the interface was observed, and the first B site layer at the interface was found to be almost formed by the Cu atomic layer as the random structure, followed by formation of the layered structure.

In addition, HAADF‐STEM images indicate that the thin film is not single crystalline, but some irregular structures were observed to grow around the interface near atomic steps of the substrate of SrTiO3. Therefore, the steps largely affect the growth process of the thin film.
Formation process of β‐FeSi2 from amorphous Fe‐Si synthesized by ion implantation: Fe concentration dependence
Authors: NAITO M. , ISHIMARU M.
Published: October 2009

Formation processes of β‐FeSi2 from amorphous Fe‐Si layers have been investigated using transmission electron microscopy (TEM). Si(111) substrates were irradiated with 120 keV Fe ions at −150°C to fluences of 1.0 × 1017 and 4.0 × 1017 cm–2. An amorphous Fe‐Si layer embedded in an amorphous Si was formed in the low‐fluence sample, whereas an amorphous Fe‐Si surface layer on an amorphous Si was obtained in the high‐fluence one. The amorphous Fe‐Si layers were crystallized to β‐FeSi2 after thermal annealing at 800°C for 2 h. Cross‐sectional and plan‐view TEM observations revealed that, prior to the formation of β‐FeSi2, the amorphous Fe‐Si layers crystallized to α‐FeSi2 in the low‐fluence sample and to ɛ‐FeSi in the high‐fluence one. The absence of metastable γ‐FeSi2 which is considered as a precursor of epitaxially grown β‐FeSi2 on Si was attributed to the instability of γ‐phase in an amorphous matrix.
TEM, HRTEM, electron holography and electron tomography studies of γ′ and γ″ nanoparticles in Inconel 718 superalloy
Authors: DUBIEL B. , KRUK A. , STEPNIOWSKA E. , CEMPURA G. , GEIGER D. , FORMANEK P. , HERNANDEZ J. , MIDGLEY P. , CZYRSKA‐FILEMONOWICZ A.
Published: October 2009

The aim of the study was the identification of γ′ and γ″ strengthening precipitates in a commercial nickel‐base superalloy Inconel 718 (Ni‐19Fe‐18Cr‐5Nb‐3Mo‐1Ti‐0.5Al‐0.04C, wt %) using TEM dark‐field, HRTEM, electron holography and electron tomography imaging. To identify γ′ and γ″ nanoparticles unambiguously, a systematic analysis of experimental and theoretical diffraction patterns were performed. Using HRTEM method it was possible to analyse small areas of precipitates appearance. Electron holography and electron tomography techniques show new possibilities of visualization of γ′ and γ″ nanoparticles. The analysis by means of different complementary TEM methods showed that γ″ particles exhibit a shape of thin plates, while γ′ phase precipitates are almost spherical.
Tensorial Minkowski functionals and anisotropy measures for planar patterns
Authors: SCHRÖDER‐TURK G.E. , KAPFER S. , BREIDENBACH B. , BEISBART C. , MECKE K.
Published: October 2009

Quantitative measures for anisotropic characteristics of spatial structure are needed when relating the morphology of microstructured heterogeneous materials to tensorial physical properties such as elasticity, permeability and conductance. Tensor‐valued Minkowski functionals, defined in the framework of integral geometry, provide a concise set of descriptors of anisotropic morphology. In this article, we describe the robust computation of these measures for microscopy images and polygonal shapes. We demonstrate their relevance for shape description, their versatility and their robustness by applying them to experimental data sets, specifically microscopy data sets of non‐equilibrium stationary Turing patterns and the shapes of ice grains from Antarctic cores.
Improvement of the pore trapping method to immobilize vital coccoid bacteria for high‐resolution AFM: a study of Staphylococcus aureus
Authors: TURNER R.D. , THOMSON N.H. , KIRKHAM J. , DEVINE D.
Published: October 2009

Preparation of vital bacteria for atomic force microscope study under aqueous fluid, such as physiological buffer or bacterial growth medium, presents challenges as cells will often desorb from the supporting surface or be dislodged by the atomic force microscope tip during imaging. An established method of immobilizing coccoid bacteria is to trap cells in polycarbonate track etched filter pores. We have significantly improved this method by modifying the pore diameter of commercially available filters to correspond to the diameter of the target strain, enabling high‐resolution imaging of stationary organisms under buffer and dividing organisms under growth media.
Automatic twin statistics from electron backscattered diffraction data
Authors: MARSHALL P.E. , PROUST G. , ROGERS J.T. , MCCABE R.J.
Published: October 2009

A new computer code has been developed to automatically extract quantitative twin statistics from electron backscatter diffraction data. The new code is an improvement upon previous codes in that it handles materials of any crystal symmetry, type I, Type II and compound twins, and general stress states. Moreover, accuracy of the results has been greatly improved. In addition, twin statistics including number, area fraction, twin thickness and twinning dependencies on orientation, grain size and neighbourhood effects can be routinely analysed. The new code has been applied to scan data from deformed magnesium, zirconium and uranium, and can potentially be used for any twinning material for which reliable electron backscatter diffraction results can be obtained.
Severe cutaneous reactions caused by barbiturates in seven Iranian children
Authors: Mamishi Setareh , Fattahi Fatemeh , Pourpak Zahra , Aghaee Farzaneh Mirza , Moinfar Zeinab , Mohammadi Mahmoud , Ashrafi Mahmoud , Moin Mostafa
Published: October 2009

Background The severe adverse cutaneous reactions of erythema multiforme (EM), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous diseases associated with significant morbidity and mortality. The most common cause is antiepileptic drugs, particularly carbamazepine and lamotrigine, as well as the barbiturates group (phenobarbital and phenytoin). In this article, we present seven children with severe adverse cutaneous reactions caused by barbiturates.

Case Reports The age of the affected children was between 2 and 11 years and they all had a history of taking barbiturates. Their symptoms started 1–3 weeks after the initiation of barbiturates, including a prodrome characterized by 2–3 days of malaise, fever, cough and anorexia, after which the skin and mucosal lesions appeared and worsened. The skin lesions varied from rash to large bullae, plus different forms of mucous membrane involvement. The offending drugs (barbiturates) were stopped immediately and care was largely supportive.

Conclusion As a result of the morbidity and/or mortality associated with EM, SJS and TEN, physicians should keep in mind their differential diagnosis when cutaneous reactions are observed in patients undergoing barbiturate therapy. Furthermore, although TEN and SJS are life‐threatening diseases, early detection and appropriate care can lead to a decrease in the incidence of death. The strategies described here seem to be successful and safe because, despite the serious conditions, our patients responded well. All survived.