bluuebunny/crossref_metadata_2025 huggingface dataset:
Explicit upper bounds for 𝐿-functions on the critical line
Authors: Chandee Vorrapan
Published: August 2009

We find an explicit upper bound for general

L
L

-functions on the critical line, assuming the Generalized Riemann Hypothesis, and give as illustrative examples its application to some families of

L
L

-functions and Dedekind zeta functions. Further, this upper bound is used to obtain lower bounds beyond which all eligible integers are represented by Ramanujan’s ternary form and Kaplansky’s ternary forms. This improves on previous work by Ono and Soundararajan on Ramanujan’s form and by Reinke on Kaplansky’s forms with a substantially easier proof.
Sec22b Is a Negative Regulator of Phagocytosis in Macrophages
Authors: Hatsuzawa Kiyotaka , Hashimoto Hitoshi , Hashimoto Hiromi , Arai Seisuke , Tamura Taku , Higa-Nishiyama Arisa , Wada Ikuo
Published: August 2009

The endoplasmic reticulum (ER) is proposed to be a membrane donor for phagosome formation. In support of this, we have previously shown that the expression level of syntaxin 18, an ER-localized SNARE protein, correlates with phagocytosis activity. To obtain further insights into the involvement of the ER in phagocytosis we focused on Sec22b, another ER-localized SNARE protein that is also found on phagosomal membranes. In marked contrast to the effects of syntaxin 18, we report here that phagocytosis was nearly abolished in J774 macrophages stably expressing mVenus-tagged Sec22b, without affecting the cell surface expression of the Fc receptor or other membrane proteins related to phagocytosis. Conversely, the capacity of the parental J774 cells for phagocytosis was increased when endogenous Sec22b expression was suppressed. Domain analyses of Sec22b revealed that the R-SNARE motif, a selective domain for forming a SNARE complex with syntaxin18 and/or D12, was responsible for the inhibition of phagocytosis. These results strongly support the ER-mediated phagocytosis model and indicate that Sec22b is a negative regulator of phagocytosis in macrophages, most likely by regulating the level of free syntaxin 18 and/or D12 at the site of phagocytosis.
Structural coloration in a fossil feather
Authors: Vinther Jakob , Briggs Derek E. G. , Clarke Julia , Mayr Gerald , Prum Richard O.
Published: August 2009

Investigation of feathers from the famous Middle Eocene Messel Oil Shale near Darmstadt, Germany shows that they are preserved as arrays of fossilized melanosomes, the surrounding beta-keratin having degraded. The majority of feathers are preserved as aligned rod-shaped eumelanosomes. In some, however, the barbules of the open pennaceous, distal portion of the feather vane are preserved as a continuous external layer of closely packed melanosomes enclosing loosely aligned melanosomes. This arrangement is similar to the single thin-film nanostructure that generates an iridescent, structurally coloured sheen on the surface of black feathers in many lineages of living birds. This is, to our knowledge, the first evidence of preservation of a colour-producing nanostructure in a fossil feather and confirms the potential for determining colour differences in ancient birds and other dinosaurs.
Daily torpor in mice: high foraging costs trigger energy-saving hypothermia
Authors: Schubert Kristin A. , Boerema Ate S. , Vaanholt Lobke M. , de Boer Sietse F. , Strijkstra Arjen M. , Daan Serge
Published: August 2009

Many animal species employ natural hypothermia in seasonal (hibernation) and daily (torpor) strategies to save energy. Facultative daily torpor is a typical response to fluctuations in food availability, but the relationship between environmental quality, foraging behaviour and torpor responses is poorly understood. We studied body temperature responses of outbred ICR (CD-1) mice exposed to different food reward schedules, simulating variation in habitat quality. Our main comparison was between female mice exposed to low foraging-cost environments and high-cost environments. As controls, we pair-fed a group of inactive animals (no-cost treatment) the same amount of pellets as high-cost animals. Mice faced with high foraging costs were more likely to employ torpor than mice exposed to low foraging costs, or no-cost controls (100% versus 40% and 33% of animals, respectively). While resting-phase temperature showed a non-significant decrease in high-cost animals, torpor was not associated with depressions in active-phase body temperature. These results demonstrate (i) that mice show daily torpor in response to poor foraging conditions; (ii) that torpor incidence is not attributable to food restriction alone; and (iii) that high levels of nocturnal activity do not preclude the use of daily torpor as an energy-saving strategy. The finding that daily torpor is not restricted to conditions of severe starvation puts torpor in mice in a more fundamental ecological context.
Parasites—the new frontier: celebrating Darwin 200
Authors: Schmid-Hempel Paul
Published: August 2009

To Darwin, parasites were fascinating examples of adaptation but their significance as selective factors for a wide range of phenomena has only been studied in depth over the last few decades. This work has had its roots in behavioural/evolutionary ecology on the one hand, and in population biology/ecology on the other, thus shaping a new comprehensive field of ‘evolutionary parasitology’. Taking parasites into account has been a success story and has shed new light on several old questions such as sexual selection, the evolution of sex and recombination, changes in behaviour, adaptive life histories, and so forth. In the process, the topic of ecological immunology has emerged, which analyses immune defences in a framework of costs and benefits. Throughout, a recurrent theme is how to appropriately integrate the underlying mechanisms as evolved boundary conditions into a framework of studying the adaptive value of traits. On the conceptual side, major questions remain and await further study.
Darwin and the popularization of evolution
Authors: Lightman Bernard
Published: August 2009

Evolution was popularized from 1860 to 1900 in the USA and Britain in a wide variety of media. Here I investigate traditional texts associated with the intellectual elite, including philosophical or scientific monographs, sermons, and published lectures. Evolution was rarely popularized in ways that reflected Darwin's major contribution to biology, his theory of natural selection. This meant that the reading audience more often encountered an alternative to Darwin's naturalistic, non-directional and non-progressive evolutionary perspective. There were at least four different versions of evolution circulating in the period from 1860 to 1900, and only one conformed to Darwin's vision.
Joseph Lister: first use of a bacterium as a ‘model organism’ to illustrate the cause of infectious disease of humans
Authors: Santer Melvin
Published: August 2009

Joseph Lister's goal was to show that a pure culture of
Bacterium lactis
, normally present in milk, uniquely caused the lactic acid fermentation of milk. To demonstrate this fact he devised a procedure to obtain a pure clonal population of
B. lactis
, a result that had not previously been achieved for any microorganism. Lister equated the process of fermentation with infectious disease and used this bacterium as a model organism, demonstrating its role in fermentation; from this result he made the inductive inference that infectious diseases of humans are the result of the growth of specific, microscopic, living organisms in the human host.
Dense-shell glycodendrimers: UV/Vis and electron paramagnetic resonance study of metal ion complexation
Authors: Appelhans Dietmar , Oertel Ulrich , Mazzeo Roberto , Komber Hartmut , Hoffmann Jan , Weidner Steffen , Brutschy Bernhard , Voit Brigitte , Francesca Ottaviani Maria
Published: August 2009

The development of dendritic metal ion carrier systems for use in a biological environment is a challenging task as the carrier system must possess multiple features (e.g. a protective shell for metal decomplexation, targeting functions, metal–intradendrimer complexes, etc.) to substitute for the function of metal proteins in processes such as copper metabolism. Thus, Cu(II) complexation by a series of poly(propyleneimine) glycodendrimers ranging up to the fifth generation that have either a dense maltose or maltotriose shell was investigated by UV/Vis spectroscopy and electron paramagnetic resonance (EPR). As a necessary step towards potential biological application, we elucidated the complexation capacity, location of the Cu(II)–dendrimer complexes and the Cu(II) coordination sphere in the dendritic environment. A generation-dependent Cu(II) complexation was found. Furthermore, analysis of the EPR spectra revealed that internal and external Cu(II) coordination and the symmetry (axial and rhombic) of the generated complexes depend on the oligosaccharide shell, dendrimer generation and the relative concentrations of Cu(II) and the dendrimers. Both axial and rhombic symmetries are generation dependent, but also distort with increasing generation number. External coordination of Cu(II) is supported by sugar groups and water molecules. Finally, a third-generation dendrimer with a maltose shell was used to explore the general complexation behaviour of the dendritic poly(propyleneimine) scaffold towards different metal ions [Cu(II), Ag(I), VO(IV), Ni(II), Eu(III) and UO2(VI)].
The sweet spot of a biological hammer: the centre of percussion of glyptodont (Mammalia: Xenarthra) tail clubs
Authors: Blanco R. Ernesto , Jones Washington W. , Rinderknecht Andrés
Published: August 2009

The importance of the centre of percussion (CP) of some hand-held sporting equipment (such as tennis rackets and baseball bats) for athletic performance is well known. In order to avoid injuries it is important that powerful blows are located close to the CP. Several species of glyptodont (giant armoured mammals) had tail clubs that can be modelled as rigid beams (like baseball bats) and it is generally assumed that these were useful for agonistic behaviour. However, the variation in tail club morphology among known genera suggests that a biomechanical and functional analysis of these structures could be useful. Here, we outline a novel method to determine the CP of the glyptodont tail clubs. We find that the largest species had the CP very close to the possible location of horny spikes. This is consistent with the inference that they were adapted to delivering powerful blows at that point. Our new analysis reinforces the case for agonistic use of tail clubs in several glyptodont species.
Prudent sperm use by leaf-cutter ant queens
Authors: den Boer Susanne P. A. , Baer Boris , Dreier Stephanie , Aron Serge , Nash David R. , Boomsma Jacobus J.
Published: August 2009

In many species, females store sperm between copulation and egg fertilization, but the consequences of sperm storage and patterns of sperm use for female life history and reproductive success have not been investigated in great detail. In hymenopteran insect societies (ants, bees, wasps), reproduction is usually monopolized by one or relatively few queens, who mate only during a brief period early in life and store sperm for later use. The queens of some ants are particularly long-lived and have the potential to produce millions of offspring during their life. To do so, queens store many sperm cells, and this sperm must remain viable throughout the years of storage. Queens should also be under strong selection to use stored sperm prudently when fertilizing eggs. We used the leaf-cutter ant
Atta colombica
to investigate the dynamics of sperm use during egg fertilization. We show that queens are able to fertilize close to 100 per cent of the eggs and that the average sperm use per egg is very low, but increases with queen age. The robustness of stored sperm was found to decrease with years of storage, signifying that senescence affects sperm either directly or indirectly via the declining glandular secretions or deteriorating sperm-storage organs. We evaluate our findings with a heuristic model, which suggests that the average queen has sperm for almost 9 years of normal colony development. We discuss the extent to which leaf-cutter ant queens have been able to optimize their sperm expenditure and infer that our observed averages of sperm number, sperm robustness and sperm use are consistent with sperm depletion being a significant cause of mortality of mature colonies of
Atta
leaf-cutter ants.
Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbα
Authors: Wu Nan , Yin Lei , Hanniman Elyisha A. , Joshi Shree , Lazar Mitchell A.
Published: August 2009

Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbα tightly controls the level of its own ligand. Heme binding to Rev-erbα recruits the NCoR/histone deacetylase 3 (HDAC3) corepressor complex to repress the transcription of the coactivator PGC-1α, a potent inducer of heme synthesis. Depletion of Rev-erbα derepresses PGC-1α, resulting in increased heme levels. Conversely, increased Rev-erbα reduces intracellular heme, and impairs mitochondrial respiration in a heme-dependent manner. Consistent with this bioenergetic impairment, overexpression of Rev-erbα dramatically inhibits cell growth due to a cell cycle arrest. Thus, Rev-erbα modulates the synthesis of its own ligand in a negative feedback pathway that maintains heme levels and regulates cellular energy metabolism.
Most Water in the Tomato Truss Is Imported through the Xylem, Not the Phloem: A Nuclear Magnetic Resonance Flow Imaging Study
Authors: Windt Carel W. , Gerkema Edo , Van As Henk
Published: August 2009

In this study, we demonstrate nuclear magnetic resonance flow imaging of xylem and phloem transport toward a developing tomato (Solanum lycopersicum) truss. During an 8-week period of growth, we measured phloem and xylem fluxes in the truss stalk, aiming to distinguish the contributions of the two transport tissues and draw up a balance between influx and efflux. It is commonly estimated that about 90% of the water reaches the fruit by the phloem and the remaining 10% by the xylem. The xylem is thought to become dysfunctional at an early stage of fruit development. However, our results do not corroborate these findings. On the contrary, we found that xylem transport into the truss remained functional throughout the 8 weeks of growth. During that time, at least 75% of the net influx into the fruit occurred through the external xylem and about 25% via the perimedullary region, which contains both phloem and xylem. About one-half of the net influx was lost due to evaporation. Halfway through truss development, a xylem backflow appeared. As the truss matured, the percentage of xylem water that circulated into the truss and out again increased in comparison with the net uptake, but no net loss of water from the truss was observed. The circulation of xylem water continued even after the fruits and pedicels were removed. This indicates that neither of them was involved in generating or conducting the circulation of sap. Only when the main axis of the peduncle was cut back did the circulation stop.
Arabidopsis Putative Selenium-Binding Protein1 Expression Is Tightly Linked to Cellular Sulfur Demand and Can Reduce Sensitivity to Stresses Requiring Glutathione for Tolerance
Authors: Hugouvieux Véronique , Dutilleul Christelle , Jourdain Agnès , Reynaud Florie , Lopez Véronique , Bourguignon Jacques
Published: August 2009

Selenium-Binding Protein1 (SBP1) gene expression was studied in Arabidopsis (Arabidopsis thaliana) seedlings challenged with several stresses, including cadmium (Cd), selenium {selenate [Se(VI)] and selenite [Se(IV)]}, copper (Cu), zinc (Zn), and hydrogen peroxide (H2O2) using transgenic lines expressing the luciferase (LUC) reporter gene under the control of the SBP1 promoter. In roots and shoots of SBP1∷LUC lines, LUC activity increased in response to Cd, Se(VI), Cu, and H2O2 but not in response to Se(IV) or Zn. The pattern of expression of SBP1 was similar to that of PRH43, which encodes the 5′-Adenylylphosphosulfate Reductase2, a marker for the induction of the sulfur assimilation pathway, suggesting that an enhanced sulfur demand triggers SBP1 up-regulation. Correlated to these results, SBP1 promoter showed enhanced activity in response to sulfur starvation. The sulfur starvation induction of SBP1 was abolished by feeding the plants with glutathione (GSH) and was enhanced when seedlings were treated simultaneously with buthionine sulfoxide, which inhibits GSH synthesis, indicating that GSH level participates in the regulation of SBP1 expression. Changes in total GSH level were observed in seedlings challenged with Cd, Se(VI), and H2O2. Accordingly, cad2-1 seedlings, affected in GSH synthesis, were more sensitive than wild-type plants to these three stresses. Moreover, wild-type and cad2-1 seedlings overexpressing SBP1 showed a significant enhanced tolerance to Se(VI) and H2O2 in addition to the previously described resistance to Cd, highlighting that SBP1 expression decreases sensitivity to stress requiring GSH for tolerance. These results are discussed with regard to the potential regulation and function of SBP1 in plants.
Order–disorder of oxygen anions and vacancies in solid solutions of La2TiO5 and La4Ga2O9
Authors: Kasunič Marta , Meden Anton , Škapin Srečo D. , Suvorov Danilo , Golobič Amalija
Published: August 2009

Successful Rietveld refinements of seven compounds with the formulae La2Ti(1−x)Ga
x
O(5−x/2), where x = 0.00, 0.20, 0.50, 0.70, 0.90, 0.95 and 1.00, were performed in order to describe the solid solubility between orthorhombic (Pnam) La2TiO5 and monoclinic (P21/c) La4Ga2O9. The relationship between the end-member structures, which are already known, is discussed; the space-group change is a consequence of ordering the oxygen vacancies that become more numerous as Ga is substituted for Ti. The structures of the solid solutions are also described. The lengths of cell edges obey Vegard's rule.
Structure of caesium disulfate at 120 and 273 K
Authors: Ståhl Kenny , Berg Rolf W. , Eriksen K. Michael , Fehrmann Rasmus
Published: August 2009

The crystal structures of Cs2S2O7 at 120 and 273 K have been determined from X-ray single-crystal data. Caesium disulfate represents a new structure type with a uniquely high number of independent formula units at 120 K: In one part caesium ions form a tube surrounding the disulfate ions, [Cs8(S2O7)6+]
n
; in the other part a disulfate double-sheet sandwiches a zigzagging caesium ion chain, [Cs2(S2O7)6−]
n
. Caesium disulfate shows an isostructural order–disorder transition between 230 and 250 K, where two disulfate groups become partially disordered above 250 K. The Cs+-ion arrangement shows a remarkable similarity to the high-pressure RbIV metal structure.
Genome‐wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage
Authors: Nishiyama Naotaka , Arai Eri , Chihara Yoshitomo , Fujimoto Hiroyuki , Hosoda Fumie , Shibata Tatsuhiro , Kondo Tadashi , Tsukamoto Taiji , Yokoi Sana , Imoto Issei , Inazawa Johji , Hirohashi Setsuo , Kanai Yae
Published: August 2009

To clarify genome‐wide DNA methylation profiles during multistage urothelial carcinogenesis, bacterial artificial chromosome (BAC) array‐based methylated CpG island amplification (BAMCA) was performed in 18 normal urothelia obtained from patients without urothelial carcinomas (UCs) (C), 17 noncancerous urothelia obtained from patients with UCs (N), and 40 UCs. DNA hypo‐ and hypermethylation on multiple BAC clones was observed even in N compared to C. Principal component analysis revealed progressive DNA methylation alterations from C to N, and to UCs. DNA methylation profiles in N obtained from patients with invasive UCs were inherited by the invasive UCs themselves, that is DNA methylation alterations in N were correlated with the development of more malignant UCs. The combination of DNA methylation status on 83 BAC clones selected by Wilcoxon test was able to completely discriminate N from C, and diagnose N as having a high risk of carcinogenesis, with 100% sensitivity and specificity. The combination of DNA methylation status on 20 BAC clones selected by Wilcoxon test was able to completely discriminate patients who suffered from recurrence after surgery from patients who did not. The combination of DNA methylation status for 11 BAC clones selected by Wilcoxon test was able to completely discriminate patients with UCs of the renal pelvis or ureter who suffered from intravesical metachronous UC development from patients who did not. Genome‐wide alterations of DNA methylation may participate in urothelial carcinogenesis from the precancerous stage to UC, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication. (Cancer Sci 2009)
Association of TP53 and MDM2 polymorphisms with survival in bladder cancer patients treated with chemoradiotherapy
Authors: Shinohara Asano , Sakano Shigeru , Hinoda Yuji , Nishijima Jun , Kawai Yoshihisa , Misumi Taku , Nagao Kazuhiro , Hara Takahiko , Matsuyama Hideyasu
Published: August 2009

Platinum‐based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle‐invasive bladder cancer. However, CRT might diminish survival as a result of the delay in cystectomy for some patients with non‐responding bladder tumors. Because the p53 tumor suppression pathway, including its MDM2 counterpart, is important in chemotherapy‐ and radiotherapy‐associated effects, functional polymorphisms in the TP53 and MDM2 genes could influence the response to treatment and the prognosis following CRT. We investigated associations between two such polymorphisms, and p53 overexpression, and response or survival in bladder cancer patients treated with CRT. The study group comprised 96 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine > proline) and MDM2 (SNP309, T > G) were genotyped using PCR‐RFLP, and nuclear expression levels of p53 were examined using immunohistochemistry. None of the genotypes or p53 overexpression was significantly associated with response to CRT. However, patients with MDM2 T / G + G / G genotypes had improved cancer‐specific survival rates after CRT (P = 0.009). In multivariate analysis, the MDM2 T / G + G / G genotypes, and more than two of total variant alleles in TP53 and MDM2, were independently associated with improved cancer‐specific survival (P = 0.031 and P = 0.015, respectively). In addition, MDM2 genotypes were significantly associated with cystectomy‐free survival (P = 0.030). These results suggest that the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer, helping patient selection for bladder conservation therapy. (Cancer Sci 2009; 100: 2376–2382)
Sexuality and personal relationships for people with an intellectual disability. Part I: service‐user perspectives
Authors: Healy E. , McGuire B. E. , Evans D. S. , Carley S. N.
Published: August 2009

Background  Despite a recent ideological shift towards the recognition of sexual autonomy for people with an intellectual disability (ID), there are continuing social and cultural barriers to sexual expression. Part I of the current two‐part study assessed the sexual knowledge, experiences and aspirations of service users through focus groups and also examined their perceptions of impediments to achieving sexual autonomy.

Method  Thirty‐two participants (20 male, 12 female) attending an ID service participated in focus groups delineated by gender and age group (13–17 years; 18–30 years; 31+ years).

Results  Analysis of the focus groups showed that service users, especially those over the age of 18 years, had an understanding of their sexual rights but also identified a number of social and cultural barriers that they felt prevent them from achieving sexual autonomy. Those under the age of 18 years had only rudimentary knowledge of sexuality issues, for example pregnancy and sexual anatomy, but aspired to relationships and marriage similar to those over the age of 18 years. Family and staff attitudes appeared to be very influential in the views of respondents. All service users had received some form of sex education, although the benefits of such education appeared most enduring for those over 18 years.

Conclusion  Service users had an understanding of their sexual rights and the social and environmental barriers that prevent them from fulfilling their rights. The provision of sex education training and promotion of positive attitudes towards appropriate sexual expression is critical to the realization of sexual autonomy for people with an ID.
A novel simple extracellular leucine‐rich repeat (eLRR) domain protein from rice (OsLRR1) enters the endosomal pathway and interacts with the hypersensitive‐induced reaction protein 1 (OsHIR1)
Authors: ZHOU LIANG , CHEUNG MING‐YAN , ZHANG QI , LEI CAI‐LIN , ZHANG SHI‐HONG , SUN SAMUEL SAI‐MING , LAM HON‐MING
Published: August 2009

Receptor‐like protein kinases (RLKs) containing an extracellular leucine‐rich repeat (eLRR) domain, a transmembrane domain and a cytoplasmic kinase domain play important roles in plant disease resistance. Simple eLRR domain proteins structurally resembling the extracellular portion of the RLKs may also participate in signalling transduction and plant defence response. Yet the molecular mechanisms and subcellular localization in regulating plant disease resistance of these simple eLRR domain proteins are still largely unclear. We provided the first experimental evidence to demonstrate the subcellular localization and trafficking of a novel simple eLRR domain protein (OsLRR1) in the endosomal pathway, using both confocal and electron microscopy. Yeast two‐hybrid and in vitro pull‐down assays show that OsLRR1 interacts with the rice hypersensitive‐induced response protein 1 (OsHIR1) which is localized on plasma membrane. The interaction between LRR1 and HIR1 homologs was shown to be highly conserved among different plant species, suggesting a close functional relationship between the two proteins. The function of OsLRR1 in plant defence response was examined by gain‐of‐function tests using transgenic Arabidopsis thaliana. The protective effects of OsLRR1 against bacterial pathogen infection were shown by the alleviating of disease symptoms, lowering of pathogen titres and higher expression of defence marker genes.
Co‐expression tools for plant biology: opportunities for hypothesis generation and caveats
Authors: USADEL BJÖRN , OBAYASHI TAKESHI , MUTWIL MAREK , GIORGI FEDERICO M. , BASSEL GEORGE W. , TANIMOTO MIMI , CHOW AMANDA , STEINHAUSER DIRK , PERSSON STAFFAN , PROVART NICHOLAS J.
Published: August 2009

Gene co‐expression analysis has emerged in the past 5 years as a powerful tool for gene function prediction. In essence, co‐expression analysis asks the question ‘what are the genes that are co‐expressed, that is, those that show similar expression profiles across many experiments, with my gene of interest?’. Genes that are highly co‐expressed may be involved in the biological process or processes of the query gene. This review describes the tools that are available for performing such analyses, how each of these perform, and also discusses statistical issues including how normalization of gene expression data can influence co‐expression results, calculation of co‐expression scores andPvalues, and the influence of data sets used for co‐expression analysis. Finally, examples from the literature will be presented, wherein co‐expression has been used to corroborate and discover various aspects of plant biology.
Variations in the dorso‐ventral organization of leaf structure and Kranz anatomy coordinate the control of photosynthesis and associated signalling at the whole leaf level in monocotyledonous species
Authors: SOARES‐CORDEIRO ANA SOFIA , DRISCOLL SIMON P. , PELLNY TILL K. , OLMOS ENRIQUE , ARRABAÇA MARIA CELESTE , FOYER CHRISTINE H.
Published: August 2009

Photosynthesis and associated signalling are influenced by the dorso‐ventral properties of leaves. The degree of adaxial/abaxial symmetry in stomatal numbers, photosynthetic regulation with respect to light orientation and the total section areas of the bundle sheath (BS) cells and the surrounding mesophyll (M) cells on the adaxial and abaxial sides of the vascular bundles were compared in two C4[Zea mays (maize) and Paspalum dilatatum] and one C3[Triticum turgidum (Durum wheat)] monocotyledonous species. The C3 leaves had a higher degree of dorso‐ventral symmetry than the C4 leaves. Photosynthetic regulation was the same on each side of the wheat leaves, as were stomatal numbers and the section area of the BS relative to that of the M cells (BS/M section area ratio). In contrast, photosynthetic regulation in maize and P. dilatatum leaves showed a marked surface‐specific response to light orientation. Compared to the adaxial sides of the C4 monocotyledonous leaves, the abaxial surfaces had more stomata and the BS/M section area ratio was significantly higher. Differences in dorso‐ventral structure, particularly in Kranz anatomy, serve not only to maximize photosynthetic capacity with respect light orientation in C4 monocotyledonous leaves but also allow adaxial and abaxial‐specific signalling from the respective M cells.
Persistence with asthma treatment is low in Germany especially for controller medication – a population based study of 483 051 patients
Authors: Hasford J. , Uricher J. , Tauscher M. , Bramlage P. , Virchow J. C.
Published: August 2009

To cite this article: Hasford J, Uricher J, Tauscher M, Bramlage P, Virchow JC. Persistence with asthma treatment is low in Germany especially for controller medication – a population based study of 483 051 patients. Allergy 2010; 65: 347–354.

Background:  The objective of the present analysis was to evaluate treatment patterns and persistence with treatment of an unselected patient population with a diagnosis of asthma.

Methods:  The database of the Bavarian statutory health insurance physician’s association (Kassenärztliche Vereinigung) covering 83% of the population was analyzed for an index period from April 2005 to March 2006. Defined daily doses (DDDs) were used to quantify treatment persistence. Results were compared with recent guidelines.

Results:  The prevalence of physician diagnosed asthma in Bavaria was 4.8% in females and 4.5% in males; only 61.4% of these patients (of a total of n = 483 051) received any anti‐asthmatic pharmacotherapy; 68.3% received medical care from their general practitioner, and 8.3% from a pulmonologist alone. Most patients (65.1%) received no more than 90 DDDs of controller medication in the index period of 365 days, only about 1% received medication for the complete index period. Long‐ (40.1%) and short‐acting β2‐agonists (65.6%) were used more frequently than inhaled corticosteroids (ICS). 52.8% of asthma patients were treated in accordance with guidelines.

Conclusions:  Persistence of asthma patients with medical treatment is low, especially for controller medication. The discrepancy between current knowledge, guidelines and clinical practice is substantial and may question the value of current guidelines for the treatment of patients with asthma in ambulatory care. In addition, the results of this study cast doubt on the impact of contemporary treatment on the decline of asthma mortality seen in recent years in Germany.
Review of calciphylaxis and treatment of a severe case after kidney transplantation with iloprost in combination with hyperbaric oxygen and cultured autologous fibrin‐based skin substitutes
Authors: Alikadic Nadja , Kovac Damjan , Krasna Metka , Lindic Jelka , Sabovic Miso , Tomazic Janez , Jeras Matjaz , Smrke Dragica
Published: August 2009

Abstract:  Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare complication in patients with end‐stage renal disease as well as in patients after renal transplantation. It should be suspected in patients with typical painful violaceous skin lesions on the extremities or on the trunk. Active multidisciplinary management approach, with intensive local wound care, is vital in these patients. Controlling parathyroid hormone, hyperbaric oxygenation, sodium thiosulphate, bisphosphonates, cinacalcet and skin grafting could be effective. In our report, we describe a case of CUA in a 43‐year‐old patient two years after kidney transplantation. Despite intensive standard treatment, his wounds progressed; therefore, we decided to use iloprost, in combination with hyperbaric oxygenation. The clean wounds were then covered with cultivated autologous skin cells to enhance wound epithelialization. Seven months after finishing iloprost and hyperbaric oxygen treatment and the first application of skin substitute, the wounds healed completely and remained healed during the four‐yr follow‐up period. We conclude that in patients with severe CUA‐induced wounds, the combined treatment with iloprost, hyperbaric oxygen and autologous cultured fibrin‐based skin substitutes can be effective. A combination of different treatment modalities is vital in patients with CUA.
Hepatocellular MxA protein expression supports the differentiation of recurrent hepatitis C disease from acute cellular rejection after liver transplantation
Authors: MacQuillan Gerry C. , de Boer W. Bastiaan , Allan Jane E. , Platten Michael A. , Reed William D. , Jeffrey Gary P.
Published: August 2009

MacQuillan GC, de Boer WB, Allan JE, Platten MA, Reed WD, Jeffrey GP. Hepatocellular MxA protein expression supports the differentiation of recurrent hepatitis C disease from acute cellular rejection after liver transplantation. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01068.x © 2009 John Wiley & Sons A/S.

Abstract:  Differentiation of recurrent hepatitis C virus (HCV) disease from acute cellular rejection (ACR) following liver transplantation can be difficult. Previously, we have found that MxA protein, a specific and sensitive marker for type 1 interferon production, is strongly expressed in chronic HCV disease. Here, we investigate MxA expression as a marker for recurrent HCV disease in the livers of 14 adult HCV patients who underwent liver transplantation. Serial liver biopsies available for 12 of these patients were stained for MxA protein and scored using a semi‐quantitative approach. Hepatocellular MxA protein levels were significantly up‐regulated (p = 0.025) in recurrent HCV disease in comparison to ACR. In biopsies that showed histological changes consistent with recurrent HCV disease, strong hepatocellular MxA staining was present in 14/18 (78%). In the liver biopsies with histological evidence of ACR, strong MxA hepatocellular staining was present in only three of 10 (30%). Thus, assessment of hepatocellular MxA protein expression can contribute to the differential diagnosis of ACR and recurrent HCV disease following liver transplantation. In conclusion, analysis of intrahepatic MxA levels has the potential to reduce the inappropriate use with high‐dose pulsing of steroids post‐operatively.
The impact of invasive fungal diseases on survival after lung transplantation
Authors: Arthurs Supha K. , Eid Albert J. , Deziel Paul J. , Marshall William F. , Cassivi Stephen D. , Walker Randall C. , Razonable Raymund R.
Published: August 2009

Arthurs SK, Eid AJ, Deziel PJ, Marshall WF, Cassivi SD, Walker RC, Razonable RR. The impact of invasive fungal diseases on survival after lung transplantation. Clin Transplant 2010: 24: 341–348. © 2009 John Wiley & Sons A/S.

Abstract:  Background:  Recipients of lung transplants are at high risk of infectious complications. We investigated the epidemiology of infections after lung transplantation and determined their impact on survival.

Methods:  We retrospectively reviewed the medical records of patients who underwent lung transplantation at Mayo Clinic (Rochester) during 1990–2005. Survival analyses were performed using Kaplan–Meier estimation and Cox proportional hazard modeling.

Results:  Sixty‐nine lung transplants were performed during the 16‐yr study period. The mean (±SD) patient age was 50.5 ± 9.7 yr; 45% were male. During the mean (±SD) follow‐up period of 1188 (±1288) d, the cumulative percentage of patients with infections were: bacteria (52%), cytomegalovirus (CMV) (49%), other viruses (32%), fungi (19%), mycobacteria (7%), and Pneumocystis jiroveci (1%). The median survival time after lung transplantation was 5.02 yr. Kaplan–Meier estimation of one‐, three‐, and five‐yr survival was 80%, 61%, and 50%, respectively. Overall, 37 (54%) patients died due to graft rejection and failure (35%), invasive fungal diseases (16%), post‐transplant lymphoproliferative disorder and other malignancies (14%), cardiovascular diseases (5%), CMV disease (3%), bacterial infection (3%), or other causes (24%). Survival analysis using Kaplan–Meier estimation showed that invasive fungal disease (Aspergillus sp., n = 9, Candida sp., n = 2, Alternaria sp., n = 1, Rhizopus sp., n = 1, and/or Mucor sp., n = 1) was significantly associated with mortality (p = 0.0104). After adjusting for age and graft rejection, invasive fungal disease remains a significant predictor of mortality (p = 0.0262).

Conclusion:  Invasive fungal disease is significantly associated with all‐cause mortality after lung transplantation. An aggressive antifungal preventive strategy may lead to improved survival after lung transplantation.
Aox gene structure, transcript variation and expression in plants
Authors: Polidoros Alexios N. , Mylona Photini V. , Arnholdt‐Schmitt Birgit
Published: August 2009

Alternative oxidase (Aox) has been proposed as a functional marker for breeding stress tolerant plant varieties. This requires presence of polymorphic Aox allele sequences in plants that affect plant phenotype in a recognizable way. In this review, we examine the hypothesis that organization of genomic Aox sequences and gene expression patterns are highly variable in relation to the possibility that such a variation may allow development of Aox functional markers in plants. Aox is encoded by a small multigene family, typically with four to five members in higher plants. The predominant structure of genomic Aox sequences is that of four exons interrupted by three introns at well conserved positions. Evolutionary intron loss and gain has resulted in the variation of intron numbers in some Aox members that may harbor two to four introns and three to five exons in their sequence. Accumulating evidence suggests that Aox gene structure is polymorphic enough to allow development of Aox markers in many plant species. However, the functional significance of Aox structural variation has not been examined exhaustively. Aox expression patterns display variability and typically Aox genes fall into two discrete subfamilies, Aox1 and Aox2, the former being present in all plants and the latter restricted in eudicot species. Typically, although not exclusively, the Aox1‐type genes are induced by many different kinds of stress, whereas Aox2‐type genes are expressed in a constitutive or developmentally regulated way. Specific Aox alleles are among the first and most intensively stress‐induced genes in several experimental systems involving oxidative stress. Differential response of Aox genes to stress may provide a flexible plan of plant defense where an energy‐dissipating system in mitochondria is involved. Evidence to link structural variation and differential allele expression patterns is scarce. Much research is still required to understand the significance of polymorphisms within AOX gene sequences for gene regulation and its potential for breeding on important agronomic traits. Association studies and mapping approaches will be helpful to advance future perspectives for application more efficiently.
Identification of regulatory elements involved in expression and induction by sucrose and UV‐B light of the Arabidopsis thaliana COX5b‐2 gene, encoding an isoform of cytochrome c oxidase subunit 5b
Authors: Comelli Raúl N. , Gonzalez Daniel H.
Published: August 2009

The promoter sequences required for expression of the Arabidopsis thaliana COX5b‐2 gene, encoding an isoform of cytochrome c oxidase subunit 5b, were analyzed using plants transformed with deleted and mutagenized forms of the promoter fused to gus. A 1000‐bp promoter fragment produces expression in root and shoot meristems, leaf and cotyledon tips, and anthers. Deletion analysis indicated the presence of positive and negative regulatory elements. A regulatory element located between −660 and −620 from the translation start site was identified as a G‐box by mutagenic analysis. Mutation of the G‐box, that is present within the coding region of the preceding gene in the genome, increases expression of COX5b‐2 in cotyledon and leaf lamina and abolishes induction by ultraviolet‐B (UV‐B) light, which presumably acts through the removal of an inhibitory factor. Identified positive regulatory elements include a site II element (TGGGCC), a related element with the sequence TGGGTC and four initiator elements (YTCANTYY) that completely abolish expression when mutated in combination. Site II elements are also involved in the response to sucrose. The results imply that the COX5b‐2 gene has retained expression characteristics presented by most respiratory chain component genes, but its expression mechanisms have diverged from those employed by COX5b‐1, the other gene encoding cytochrome c oxidase subunit 5b in Arabidopsis.
Temperature responses of substrate carbon conversion efficiencies and growth rates of plant tissues
Authors: Hansen Lee D. , Thomas Nathan R. , Arnholdt‐Schmitt Birgit
Published: August 2009

Growth rates of plant tissues depend on both the respiration rate and the efficiency with which carbon is incorporated into new structural biomass. Calorespirometric measurement of respiratory heat and CO2 rates, from which both efficiency and growth rate can be calculated, is a well established method for determining the effects of rapid temperature changes on the respiratory and growth properties of plant tissues. The effect of the alternative oxidase/cytochrome oxidase activity ratio on efficiency is calculated from first principles. Data on the temperature dependence of the substrate carbon conversion efficiency are tabulated. These data show that ε is maximum and approximately constant through the optimum growth temperature range and decreases rapidly as temperatures approach temperature limits to growth. The width of the maximum and the slopes of decreasing ε at high and low temperatures vary greatly with species, cultivars and accessions.
Autoimmune hepatitis in a demographically isolated area of Australia
Authors: Haider A. S. , Kaye G. , Thomson A.
Published: August 2009

Background: Previous studies describing autoimmune hepatitis (AIH) come from liver transplant centres in which a skewed distribution of cases may give a misleading picture of the incidence of AIH and its natural history. This series describes AIH in a stable and demographically discrete population of patients in the Australian Capital Territory (ACT) and the surrounding region.

Methods: In 42 patients with type 1 AIH (point prevalence 8 per 100 000 population), clinical, laboratory and histological features at presentation, response to initial therapy, details of maintenance therapy and outcome were recorded.

Results: Consistent with other publications, the male‐to‐female ratio was 1:3, mean age at presentation was 53 years and 24% had cirrhosis at diagnosis. Most patients (86%) responded to initial therapy and 67% went into long‐term remission. One patient died from liver failure and none required liver transplantation. Azathioprine was included in the treatment regimen in 74% of cases with doses generally <2 mg/kg. Azathioprine dose greater than or equal to 2 mg/kg was associated with better clinical outcome, but this did not reach statistical significance. A higher proportion of female patients had cirrhosis at presentation (9/10 vs 1/10; P= 0.24).

Conclusion: In this Australian community‐based study, type 1 AIH was primarily a disease of later life, responded to conventional immunosuppressive therapy and generally has a good prognosis. Further study of the use of azathioprine is warranted to determine the optimal dose.
Prior intention can locally tune inhibitory processes in the primary motor cortex: direct evidence from combined TMS‐EEG
Authors: Bonnard M. , Spieser L. , Meziane H. B. , De Graaf J. B. , Pailhous J.
Published: August 2009

Human subjects are able to prepare cognitively to resist an involuntary movement evoked by a suprathreshold transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) by anticipatory selective modulation of corticospinal excitability. Uncovering how the sensorimotor cortical network is involved in this process could reveal directly how a prior intention can tune the intrinsic dynamics of M1 before any peripheral intervention. Here, we used combined TMS‐EEG to study the cortical integrative processes that are engaged both in the preparation to react to TMS (Resist vs. Assist) and in the subsequent response to it. During the preparatory period, the contingent negative variation (CNV) amplitude was found to be smaller over central electrodes (FC1, C1, Cz) when preparing to resist compared with preparing to assist the evoked movement whereas α‐oscillation power was similar in the two conditions. Following TMS, the amplitude of the TMS evoked‐N100 component was higher in the Resist than in the Assist condition for some central electrodes (FCz, C1, Cz, CP1, CP3). Moreover, for six out of eight subjects, a single‐trial‐based analysis revealed a negative correlation between CNV amplitude and N100 amplitude. In conclusion, prior intention can tune the excitability of M1. When subjects prepare to resist a TMS‐evoked movement, the anticipatory processes cause a decreased cortical excitability by locally increasing the inhibitory processes.
Attenuated behavioural responses to acute and chronic cocaine in GASP‐1‐deficient mice
Authors: Boeuf Julien , Trigo José Manuel , Moreau Pierre‐Henri , Lecourtier Lucas , Vogel Elise , Cassel Jean‐Cristophe , Mathis Chantal , Klosen Paul , Maldonado Rafael , Simonin Frédéric
Published: August 2009

G protein‐coupled receptor (GPCR) associated sorting protein 1 (GASP‐1) interacts with GPCRs and is implicated in their postendocytic sorting. Recently, GASP‐1 has been shown to regulate dopamine (D2) and cannabinoid (CB1) receptor signalling, suggesting that preventing GASP‐1 interaction with GPCRs might provide a means to limit the decrease in receptor signalling upon sustained agonist treatment. In order to test this hypothesis, we have generated and behaviourally characterized GASP‐1 knockout (KO) mice and have examined the consequences of the absence of GASP‐1 on chronic cocaine treatments. GASP‐1 KO and wild‐type (WT) mice were tested for sensitization to the locomotor effects of cocaine. Additional mice were trained to acquire intravenous self‐administration of cocaine on a fixed ratio 1 schedule of reinforcement, and the motivational value of cocaine was then assessed using a progressive ratio schedule of reinforcement. The dopamine and muscarinic receptor densities were quantitatively evaluated in the striatum of WT and KO mice tested for sensitization and self‐administration. Acute and sensitized cocaine‐locomotor effects were attenuated in KO mice. A decrease in the percentage of animals that acquired cocaine self‐administration was also observed in GASP‐1‐deficient mice, which was associated with pronounced down‐regulation of dopamine and muscarinic receptors in the striatum. These data indicate that GASP‐1 participates in acute and chronic behavioural responses induced by cocaine and are in agreement with a role of GASP‐1 in postendocytic sorting of GPCRs. However, in contrast to previous studies, our data suggest that upon sustained receptor stimulation GASP‐1 stimulates recycling rather than receptor degradation.