bluuebunny/crossref_metadata_2025 huggingface dataset:
Educational gaming in the health sciences: systematic review
Authors: Blakely Gillian , Skirton Heather , Cooper Simon , Allum Peter , Nelmes Pam
Published: November 2008

Title.  Educational gaming in the health sciences: systematic review.

Aim.  This paper is a report of a review to investigate the use of games to support classroom learning in the health sciences.

Background.  One aim of education in the health sciences is to enable learners to develop professional competence. Students have a range of learning styles and innovative teaching strategies assist in creating a dynamic learning environment. New attitudes towards experiential learning methods have contributed to the expansion of gaming as a strategy.

Data sources.  A search for studies published between January 1980 and June 2008 was undertaken, using appropriate search terms. The databases searched were: British Education Index, British Nursing Index, The Cochrane Library, CINAHLPlus, Medline, PubMed, ERIC, PsychInfo and Australian Education Index.

Methods.  All publications and theses identified through the search were assessed for relevance. Sixteen papers reporting empirical studies or reviews that involved comparison of gaming with didactic methods were included.

Results.  The limited research available indicates that, while both traditional didactic methods and gaming have been successful in increasing student knowledge, neither method is clearly more helpful to students. The use of games generally enhances student enjoyment and may improve long‐term retention of information.

Conclusion.  While the use of games can be viewed as a viable teaching strategy, care should be exercised in the use of specific games that have not been assessed objectively. Further research on the use of gaming is needed to enable educators to gaming techniques appropriately for the benefit of students and, ultimately, patients.
Integrated health programme: a workplace randomized controlled trial
Authors: Tveito Torill H. , Eriksen Hege R.
Published: November 2008

Title.  Integrated health programme: a workplace randomized controlled trial.

Aim.  This paper is the report of a pilot study to assess if an Integrated Health Programme would reduce sick leave and subjective health complaints, and increase coping in a population of nursing personnel.

Background.  The work group in Norway with most sick leave is healthcare workers. More than 50% of the sick leave is because of subjective health complaints. Work place physical exercise interventions have a documented positive effect on sick leave.

Method.  After baseline screening, employees who had agreed to participate (n = 40) were randomized to an intervention or control group. The intervention group participated in an Integrated Health Programme twice weekly during working hours. The programme consisted of physical exercise, stress management training, health information and an examination of the participants’ workplace. The control group was offered the same intervention after the project was finished. This study was carried out from 2001 to 2002.

Findings.  There were no statistically significant effects on sick leave or health‐related quality of life. The intervention group reported fewer neck complaints compared to the control group, but otherwise there were no effects on subjective health complaints. However, the subjective effects were large and highly statistically significant, the intervention group reporting improvement in health, physical fitness, muscle pain, stress management, maintenance of health and work situation.

Conclusion.  The Integrated Health Programme was not effective in reducing sick leave and subjective health complaints, but may be of use to employers wanting to increase employee job satisfaction and well‐being.
Ethnobotanical ground‐truthing: indigenous knowledge, floristic inventories and satellite imagery in the upper Rio Negro, Brazil
Authors: Abraão Marcia Barbosa , Nelson Bruce W. , Baniwa João Cláudio , Yu Douglas W. , Shepard Jr Glenn H.
Published: November 2008

Aim  To assess the utility of indigenous habitat knowledge in studies of habitat diversity in Amazonia.

Location  Baniwa indigenous communities in Rio Içana, upper Rio Negro, Brazil.

Methods  Six campinarana vegetation types, recognized and named by a consensus of Baniwa indigenous informants according to salient indicator species, were studied in 15 widely distributed plots. Floristic composition (using Baniwa plant nomenclature only, after frustrated attempts to obtain botanical collection permits), quantitative measures of forest structure and GPS waypoints of the 4‐ha composite plot contours were registered, permitting their location on Landsat satellite images. Non‐metric multidimensional scaling (NMDS) ordination was carried out using pc‐ord software.

Results  The NMDS ordinations of the plot data revealed a clear gradient of floristic composition that was highly correlated with three quantitative measures of forest structure: basal area, canopy height and satellite reflectance.

Main conclusions  Baniwa‐defined forest types are excellent predictors of habitat diversity along the structural gradient comprising distinctive white‐sand campinarana vegetation types. Indigenous ecological knowledge, as revealed by satellite imagery and floristic analyses, proves to be a powerful and efficient shortcut to assessing habitat diversity, promoting dialogue between scientific and indigenous worldviews, and promoting joint study and conservation of biodiversity.
Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS)
Authors: Holme I. , Aastveit A. H. , Hammar N. , Jungner I. , Walldius G.
Published: November 2008

Objectives.  To compare lipoprotein components associated with ischaemic and haemorrhagic stroke by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study (n = 148 600).

Design.  Prospective follow‐up study (11.8, range 7–17 years) of fatal and nonfatal ischaemic and haemorrhagic stroke through linkage with Swedish hospital discharge and mortality registers.

Setting.  Measurements of lipoprotein components from health check‐ups in the larger Stockholm area.

Results.  Ischaemic stroke was more common than haemorrhagic stroke (5 :1), but case fatality was higher in haemorrhagic stroke. An elevated apoB/apoA‐1 ratio and triglycerides, non‐HDL cholesterol, low HDL cholesterol, and the total cholesterol to high‐density cholesterol (TC/HDL‐C) ratio were associated with increased incidence of nonfatal and fatal ischaemic stroke as well as all cerebrovascular events (n = 7480) in both genders. The associations were somewhat stronger for nonfatal than fatal events. In ischaemic stroke the apoB/apoA‐1 ratio was a stronger predictor than the TC/HDL‐C ratio in all subjects, in those below 65 years of age and in those with LDL‐C below 3 mmol L−1. Haemorrhagic stroke was not associated with elevated atherogenic lipoproteins except for increased risk of fatal haemorrhagic stroke in women with a high apoB/apoA‐I ratio.

Conclusions.  Dyslipidaemia is associated with an increased risk of ischaemic stroke but few relations were seen in haemorrhagic stroke. Use of the apoB/apoA‐I ratio as a marker of dyslipidaemia is at least as efficient as conventional lipids, for the identification of subjects at increased risk of stroke, especially ischaemic stroke. Practical advantages, fasting is not needed, speak in favour of using apoB and apoA‐1 in stroke risk prediction.
Heart rate variability, overnight urinary norepinephrine and C‐reactive protein: evidence for the cholinergic anti‐inflammatory pathway in healthy human adults
Authors: Thayer J. F. , Fischer J. E.
Published: November 2008

Objectives. C‐reactive protein (CRP) has been identified as an independent predictor of cardiovascular mortality and morbidity in population‐based studies. Recent advances have suggested a prominent role for the autonomic nervous system (ANS) in the regulation of inflammation. However, noin vivohuman studies have examined indices of sympathetic and parasympathetic nervous system activity simultaneously in relationship to inflammatory markers in apparently healthy adults. Therefore, the objective of this study was to assess the immunomodulatory effects of the ANS.

Methods and results. The study population comprised 611 apparently healthy employees of an airplane manufacturing plant in southern Germany. Urinary NE was positively associated with white blood cell count (WBC) in the total sample. We found an inverse association between indices of vagally mediated heart rate variability and plasma levels of (CRP), which was significantly larger in females than in males after controlling for relevant covariates including NE. Similar results were found using the percentage of interbeat interval differences >50 ms and WBC.

Conclusions. We report here for the first time, in a large sample of healthy human adults, evidence supporting the hypothesis of a clinically relevant cholinergic anti‐inflammatory pathway after controlling for sympathetic nervous system activity. This suggests an important role for the vagal control of systemic inflammatory activity in cardiovascular disease.
Factors associated with elevated or blunted PTH response in vitamin D insufficient adults
Authors: Gunnarsson Ö. , Indridason Ó. S. , Franzson L. , Sigurdsson G.
Published: November 2008

Objectives.  The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency.

Design.  This was a cross‐sectional study consisting of 516 healthy men and women, aged 30–85, all Caucasians with vitamin D insufficiency [serum 25(OH)D < 45 nmol L−1]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately.

Results.  We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin‐like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R2 = 0.472) but smoking, BMI and kidney function in women (R2 = 0.362).

Conclusions.  Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women.
Quality of prescription and fabrication of single‐unit crowns by general dental practitioners in Wales
Authors: JENKINS S. J. , LYNCH C. D. , SLOAN A. J. , GILMOUR A. S. M.
Published: November 2008

Summary  The aim of this investigation was to describe the quality of prescription and fabrication of single‐unit crowns by general dental practitioners in Wales. One hundred pre‐piloted questionnaires were distributed to commercial laboratories in Wales with large catchment areas, and 20 pre‐piloted questionnaires were distributed to the production laboratory at the Cardiff Dental Hospital. Information was collected relating to the quality of prescription and master impressions for single‐unit crowns. One hundred and seven completed questionnaires were returned (response rate = 89%). Sixty per cent (n = 64) of questionnaires related to single‐unit crowns being made in general practice under private funding arrangements, 30% (n = 32) were being made in general dental practice under National Health Service (public) funding arrangements and 10% (n = 11) were collected from the Dental Hospital. Polyvinylsiloxane impression material was used to record the master impression in all cases (n = 107). Plastic stock trays were used to make the master impression in 79% of cases (n = 85), metal stock trays were used in 19% of cases (n = 20) and special trays were used in 2% of cases (n = 2). Eighty‐five per cent (n = 91) of master casts were considered to be adequate for crown fabrication. Less than 50% of written instructions (n = 52) were considered ‘clear’ and of sufficient detail to adequately specify the planned crown. In 21% of cases (n = 22), the technician had to contact the dentist for clarification of the design prior to making the crown. While the quality of impression making for single‐unit crowns was of a reasonable standard, the quality of the accompanying written communication was poor and more than one‐half of written instructions examined failed to meet the requirements of the European Union Medical Devices Directive.
Phosphorylation of the RitR DNA‐binding domain by a Ser–Thr phosphokinase: implications for global gene regulation in the streptococci
Authors: Ulijasz Andrew T. , Falk Shaun P. , Weisblum Bernard
Published: November 2008

We report selective phosphorylation of the DNA‐binding domain of theStreptococcus pneumoniaetranscriptional regulator RitR. RitR is annotated as a two‐component response regulator, but lacks a cognate His kinase as a neighbouring locus in the genome. In addition, Asn replaces Asp at the expected acceptor site. By the use of combinatorial phage display, we identified PhpP, aS. pneumoniaeSer–Thr eukaryotic‐like PP2C phosphatase as an interacting partner of RitR. RitR interacts with the phage‐displayed peptide VADGMGGR which forms a part of the active‐site sequence of PhpP. RitR is phosphorylatedin vitroby StkP, the presumed cognate kinase of PhpP, and the site on RitR that is phosphorylated has been localized to the RitR DNA‐binding domain. PhpP together with its cognate kinase StkP appear to be necessary for Piu haem transporter expression.In vitrostudies suggest that PhpP and StkP interact competitively with RitR in that RitR–PhpP–piupromoter ternary complexes are disrupted by StkP. Our findings indicate a regulatory link between RitR and Ser–Thr kinase–phosphatase‐based bacterial signal transduction.
Rv1675c (cmr) regulates intramacrophage and cyclic AMP‐induced gene expression in Mycobacterium tuberculosis‐complex mycobacteria
Authors: Gazdik Michaela A. , Bai Guangchun , Wu Yan , McDonough Kathleen A.
Published: November 2008

Cyclic AMP (cAMP) has recently been shown to be a global regulator of gene expression in Mycobacterium tuberculosis (Mtb). In this study we identified a new cAMP‐associated regulon in Mtb and Mycobacterium bovis BCG, which is distinct from the previously described CRPMt regulon. Proteomic comparison of wild‐type M. bovis BCG with a Rv1675c (cmr) knockout strain showed dysregulated expression of four previously identified proteins encoded by the cAMP‐induced genes (cAIGs) mdh, groEL2, Rv1265 and PE_PGRS6a. Regulated expression of these four cAIGs also occurred during macrophage infection, and this regulation required cmr in both Mtb and M. bovis BCG. Purified His‐Cmr bound to the DNA sequences upstream of three cAIGs (mdh, groEL2, Rv1265) in electrophoretic mobility shift assays, suggesting direct regulation of these genes by Cmr. We also found that low pH stimulated cAMP production in both Mtb and M. bovis BCG, but broadly affected cAIG regulation only in M. bovis BCG. These studies identify Cmr as a transcription factor that regulates cAIGs within macrophages, and suggest that multiple factors affect cAMP‐associated gene regulation in tuberculosis‐complex mycobacteria. cAMP signalling and Cmr‐mediated gene regulation during Mtb infection of macrophages may have implications for TB pathogenesis.
Identification of a glycosylphosphatidylinositol anchor‐modifying β1‐3 N‐acetylglucosaminyl transferase in Trypanosoma brucei
Authors: Izquierdo Luis , Nakanishi Masayuki , Mehlert Angela , Machray Greg , Barton Geoffrey J. , Ferguson Michael A. J.
Published: November 2008

Trypanosoma brucei expresses complex glycoproteins throughout its life cycle. A review of its repertoire of glycosidic linkages suggests a minimum of 38 glycosyltransferase activities. Of these, five have been experimentally related to specific genes and a further nine can be associated with candidate genes. The remaining linkages have no obvious candidate glycosyltransferase genes; however, the T. brucei genome contains a family of 21 putative UDP sugar‐dependent glycosyltransferases of unknown function. One representative, TbGT8, was used to establish a functional characterization workflow. Bloodstream and procyclic‐form TbGT8 null mutants were created and both exhibited normal growth. The major surface glycoprotein of the procyclic form, the procyclin, exhibited a marked reduction in molecular weight due to changes in the procyclin glycosylphosphatidylinositol (GPI) anchor side‐chains. Structural analysis of the mutant procyclin GPI anchors indicated that TbGT8 encodes a UDP‐GlcNAc: β‐Gal‐GPI β1‐3 GlcNAc transferase. This is only the second GPI‐modifying glycosyltransferase to have been identified from any organism. The glycosylation of the major glycoprotein of bloodstream‐form T. brucei, the variant surface glycoprotein, was unaffected in the TbGT8 mutant. However, changes in the lectin binding of other glycoproteins suggest that TbGT8 influences the processing of the poly N‐acetyllactosamine‐containing asparagine‐linked glycans of this life cycle stage.
Bordetella Bsp22 forms a filamentous type III secretion system tip complex and is immunoprotective in vitro and in vivo
Authors: Medhekar Bob , Shrivastava Ruchi , Mattoo Seema , Gingery Mari , Miller Jeff F.
Published: November 2008

Type III secretion system (T3SS) tip complexes serve as adaptors that bridge the T3SS needle and the pore‐forming translocation apparatus. In this report we demonstrate that Bsp22, the most abundantly secreted substrate of the Bordetella T3SS, self‐polymerizes to form the Bordetella bronchiseptica tip complex. Bsp22 is required for both T3SS‐mediated cytotoxicity against eukaryotic cells and haemoglobin release from erythrocytes. Bacterial two‐hybrid analysis and protein pull‐down assays demonstrated the ability of Bsp22 to associate with itself and to bind BopD, a component of the Bordetella translocation pore. Immunoblot and cross‐linking analysis of secreted proteins or purified Bsp22 showed extensive multimerization which was shown by transmission electron microscopy to lead to the formation of variable length flexible filaments. Immunoelectron microscopy revealed Bsp22 filaments on the surface of bacterial cells. Given its required role in secretion and cell‐surface exposure, we tested the protective effects of antibodies against Bsp22 in vitro and in vivo. Polyclonal antisera against Bsp22 fully protected epithelial cells from T3SS‐dependent killing and immunization with Bsp22 protected mice against Bordetella infection. Of the approximately 30 genes which encode the Bordetella T3SS apparatus, bsp22 is the only one without characterized orthologues in other well‐characterized T3SS loci. A maximum likelihood phylogenetic analysis indicated that Bsp22 defines a new subfamily of T3SS tip complex proteins. Given its immunogenic and immunoprotective properties and high degree of conservation among Bordetella species, Bsp22 and its homologues may prove useful for diagnostics and next‐generation subunit vaccines.
Vacuole inheritance regulates cell size and branching frequency of Candida albicans hyphae
Authors: Veses Veronica , Richards Andrea , Gow Neil A. R.
Published: November 2008

Hyphal growth of Candida albicans is characterized by asymmetric cell divisions in which the subapical mother cell inherits most of the vacuolar space and becomes cell cycle arrested in G1, while the apical daughter cell acquires most of the cell cytoplasm and progresses through G1 into the next mitotic cell cycle. Consequently, branch formation in hyphal compartments is delayed until sufficient cytoplasm is synthesized to execute the G1 ‘START’ function. To test the hypothesis that this mode of vacuole inheritance determines cell cycle progression and therefore the branching of hyphae, eight tetracycline‐regulated conditional mutants were constructed that were affected at different stages of the vacuole inheritance pathway. Under repressing conditions, vac7, vac8 and fab1 mutants generated mycelial compartments with more symmetrically distributed vacuoles and increased branching frequencies. Repression of VAC1, VAM2 and VAM3 resulted in sparsely branched hyphae, with large vacuoles and enlarged hyphal compartments. Therefore, during hyphal growth of C. albicans the cell cycle, growth and branch formation can be uncoupled, resulting in the investment of cytoplasm to support hyphal extension at the expense of hyphal branching.
Cloning, expression and immunoprotective efficacy of rHaa86, the homologue of the Bm86 tick vaccine antigen, from Hyalomma anatolicum anatolicum
Authors: AZHAHIANAMBI P. , DE LA FUENTE J. , SURYANARAYANA V. V. S. , GHOSH S.
Published: November 2008

The Bm86 homologue of Hyalomma anatolicum anatolicum Izatnagar isolate was cloned and expressed in methylotropic yeast Pichia pastoris as intracellular, glycosylated and particulated form. It was named as rHaa86, the first recombinant protein of H. a. anatolicum. Seven epidermal growth factor‐like domains predicted in Haa86 were structurally similar with that of its Bm86 counterpart. The identity between the corresponding EGF like domains of Bm86 and Haa86 were ranging from 51·3% to 78·3%. The molecular weight of the rHaa86 was 120–140 kDa, with possible 50–70 kDa glycosylation. The purified rHaa86 was characterized immunologically and evaluated for its immunoprotective potential against homologous challenge infestation in three groups of cross‐bred calves. The immediate rejection percentage of females of H. a. anatolicum was 36 5%, 12·4% and 10·1% fed on immunized (group 1), adjuvant control (group 2) and untreated control (group 3) calves, respectively. The percent rejection of female ticks fed on immunized calves was 24·1% and 26·4% higher than for the ticks fed on control groups 2 and 3, respectively (P < 0·05). The reduction of number of females, mean weight of eggs, adult females and efficacy of immunogen were 58·0%, 9·0%, 5·0% and 61·6%, respectively. The mean reproductive index of females fed on group 1 calves was significantly lower (P < 0·05) than the females fed on the control groups and 44% reduction in the number of engorged larvae was recorded from the group 1 calves. The data demonstrated that rHaa86 antigen based vaccine could serve as one of the effective components in the integrated control of H. a. anatolicum.
Mast cell degranulation contributes to susceptibility to Leishmania major
Authors: ROMÃO P. R. T. , DA COSTA SANTIAGO H. , RAMOS C. D. L. , DE OLIVEIRA C. F. E. , MONTEIRO M. C. , DE QUEIROZ CUNHA F. , VIEIRA L. Q.
Published: November 2008

Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL‐4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN‐γ, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL‐4 KO animals, indicating that mediators other than IL‐4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.
In vitro antigen presenting cell‐derived IL‐10 and IL‐6 correlate with Trichuris muris isolate‐specific survival
Authors: D’ELIA R. , ELSE K. J.
Published: November 2008

Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist — the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate‐specific E/S with bone marrow‐derived macrophages (BMMΦ) and dendritic cells (BMDCs) in vitro. Markers of co‐stimulation and levels of MHC‐II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL‐10 and IL‐6 from both macrophages (F4/80+CD11b+CD11c−) and dendritic cells (CD11c+CD11b+F4/80−) compared to J and E isolate E/S. If these in vitro differences in APC‐derived cytokines, particularly IL‐10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective.
Biosynthetic pathways of the pheromone of the Egyptian armywormSpodoptera littoralis
Authors: MUÑOZ LOURDES , ROSELL GLORIA , QUERO CARMEN , GUERRERO ANGEL
Published: November 2008

AbstractMost insect pheromones comprise multicomponent blends of geometric or optical isomers, and one major question is how insects produce species‐specific ratios of components for successful reproductive isolation. Key enzymes suggested to be involved in pheromone biosynthesis are acetyl‐coenzyme A carboxylase and fatty acyl synthetase, chain‐shortening enzymes, desaturases, elongases, reductases, oxidases, and alcohol acetyl transferases. The female pheromone composition of the Egyptian armywormSpodoptera littoralis(Boisd.) is highly dependent on the origin of the strain. In this review, we present a summary of the different reported pheromone compositions of the moth, including from our recent studies on this subject, as well as the biosynthetic routes to the different components and the molecular approaches involved. In addition, the key role played in the proposed biosynthetic pathways by a number of important biosynthetic enzymes, such as chain shortening enzymes, desaturases and alcohol acetyl transferases, is outlined, as well as the latest developments on the inhibition of these enzymes.
Development of the cuticular wax during growth of Kalanchoe daigremontiana (Hamet et Perr. de la Bathie) leaves
Authors: VAN MAARSEVEEN CLARE , HAN HONG , JETTER REINHARD
Published: November 2008

The goal of the present study was to monitor cuticular wax accumulation during leaf development of Kalanchoe daigremontiana. Leaves expanded linearly until they were 40–60 d old. Wax coverages of leaves on the third node increased steadily during initial leaf development, from 6.5 µg·cm−2 on day 22 to 15.3 µg·cm−2 on day 53, and then levelled off. Triterpenoids dominated the wax mixture throughout leaf development, but decreased from 74 to 40–45% in mature leaves, while very long‐chain fatty acid (VLCFA) derivatives increased from 19 to 39–44%. The major VLCFA derivatives were alkanes, accompanied by fatty acids, primary alcohols, aldehydes and alkyl esters. In all compound classes, either C34 or C33 homologs predominated during leaf development. Eight different triterpenoids were identified, with glutinol constituting 70% of the fraction, and friedelin (20%) and germanicol (10%) as further major components of the young leaf wax. The glutinol percentage decreased, while the relative amounts of epifriedelanol and glutanol increased during development. Various leaf pairs upwards from the third node showed similar growth patterns and developmental time courses of cuticular wax amounts and composition. Based on these surface chemical analyses, the relative activities of biosynthetic pathways leading to various wax components can be assessed.
Accumulation of 2‐C‐methyl‐d‐erythritol 2,4‐cyclodiphosphate in illuminated plant leaves at supraoptimal temperatures reveals a bottleneck of the prokaryotic methylerythritol 4‐phosphate pathway of isoprenoid biosynthesis
Authors: RIVASSEAU CORINNE , SEEMANN MYRIAM , BOISSON ANNE‐MARIE , STREB PETER , GOUT ELISABETH , DOUCE ROLAND , ROHMER MICHEL , BLIGNY RICHARD
Published: November 2008

Metabolic profiling using phosphorus nuclear magnetic resonance (31P‐NMR) revealed that the leaves of different herbs and trees accumulate 2‐C‐methyl‐d‐erythritol 2,4‐cyclodiphosphate (MEcDP), an intermediate of the methylerythritol 4‐phosphate (MEP) pathway, during bright and hot days. In spinach (Spinacia oleracea L.) leaves, its accumulation closely depended on irradiance and temperature. MEcDP was the only 31P‐NMR‐detected MEP pathway intermediate. It remained in chloroplasts and was a sink for phosphate. The accumulation of MEcDP suggested that its conversion rate into 4‐hydroxy‐3‐methylbut‐2‐enyl diphosphate, catalysed by (E)‐4‐hydroxy‐3‐methylbut‐2‐enyl diphosphate synthase (GcpE), was limiting under oxidative stress. Indeed, O2 and ROS produced by photosynthesis damage this O2‐hypersensitive [4Fe‐4S]‐protein. Nevertheless, as isoprenoid synthesis was not inhibited, damages were supposed to be continuously repaired. On the contrary, in the presence of cadmium that reinforced MEcDP accumulation, the MEP pathway was blocked. In vitro studies showed that Cd2+ does not react directly with fully assembled GcpE, but interferes with its reconstitution from recombinant GcpE apoprotein and prosthetic group. Our results suggest that MEcDP accumulation in leaves may originate from both GcpE sensitivity to oxidative environment and limitations of its repair. We propose a model wherein GcpE turnover represents a bottleneck of the MEP pathway in plant leaves simultaneously exposed to high irradiance and hot temperature.
Water stress vulnerability of four Banksia species in contrasting ecohydrological habitats on the Gnangara Mound, Western Australia
Authors: CANHAM CAROLINE A. , FROEND RAYMOND H. , STOCK WILLIAM D.
Published: November 2008

This study investigated the interspecific differences in vulnerability to xylem embolism of four phreatophytes – two facultative phreatophytes (Banksia attenuata and B. menziesii) and two obligate phreatophytes (B. ilicifolia and B. littoralis). Species differences at the same position along an ecohydrological gradient on the Gnangara Groundwater Mound, Western Australia were determined in addition to intraspecific differences to water stress between populations in contrasting ecohydrological habitats. Stem‐ and leaf‐specific hydraulic conductivity, as well as Huber values (ratio of stem to leaf area), were also determined to support these findings. We found that where water is readily accessible, there were no interspecific differences in vulnerability to water stress. In contrast both facultative phreatophyte species were more resistant to xylem embolism at the more xeric dune crest site than at the wetter bottom slope site. B. ilicifolia did not differ in vulnerability to embolism, supporting its classification as an obligate phreatophyte. Other measured hydraulic traits (KS, KL and Huber value) showed no adaptive responses, although there was a tendency for plants at the wetter site to have higher KS and KL. This study highlights the influence site hydrological attributes can have on plant hydraulic architecture across species and environmental gradients.
Differential requirement for NO during ABA‐induced stomatal closure in turgid and wilted leaves
Authors: RIBEIRO DIMAS M. , DESIKAN RADHIKA , BRIGHT JO , CONFRARIA ANA , HARRISON JUDITH , HANCOCK JOHN T. , BARROS RAIMUNDO S. , NEILL STEVEN J. , WILSON IAN D.
Published: November 2008

Abscisic acid (ABA)‐induced stomatal closure is mediated by a complex, guard cell signalling network involving nitric oxide (NO) as a key intermediate. However, there is a lack of information concerning the role of NO in the ABA‐enhanced stomatal closure seen in dehydrated plants. The data herein demonstrate that, while nitrate reductase (NR)1‐mediated NO generation is required for the ABA‐induced closure of stomata in turgid leaves, it is not required for ABA‐enhanced stomatal closure under conditions leading to rapid dehydration. The results also show that NO signalling in the guard cells of turgid leaves requires the ABA‐signalling pathway to be both capable of function and active. The alignment of this NO signalling with guard cell Ca2+‐dependent/independent ABA signalling is discussed. The data also highlight a physiological role for NO signalling in turgid leaves and show that stomatal closure during the light‐to‐dark transition requires NR1‐mediated NO generation and signalling.
The long‐term responses of the photosynthetic proton circuit to drought
Authors: KOHZUMA KAORI , CRUZ JEFFREY A. , AKASHI KINYA , HOSHIYASU SAKI , MUNEKAGE YURI NAKAJIMA , YOKOTA AKIHO , KRAMER DAVID M.
Published: November 2008

Proton motive force (pmf) across thylakoid membranes is not only for harnessing solar energy for photosynthetic CO2 fixation, but also for triggering feedback regulation of photosystem II antenna. The mechanisms for balancing these two roles of the proton circuit under the long‐term environmental stress, such as prolonged drought, have been poorly understood. In this study, we report on the response of wild watermelon thylakoid ‘proton circuit’ to drought stress using both in vivo spectroscopy and molecular analyses of the representative photosynthetic components. Although drought stress led to enhanced proton flux via a ∼34% increase in cyclic electron flow around photosystem I (PS I), an observed ∼fivefold decrease in proton conductivity, gH+, across thylakoid membranes suggested that decreased ATP synthase activity was the major factor for sustaining elevated qE. Western blotting analyses revealed that ATP synthase content decreased significantly, suggesting that quantitative control of the complex plays a pivotal role in down‐regulation of gH+. The expression level of cytochrome b6f complex – another key control point in photosynthesis – also declined, probably to prevent excess‐reduction of PS I electron acceptors. We conclude that plant acclimation to long‐term environmental stress involves global changes in the photosynthetic proton circuit, in which ATP synthase represents the key control point for regulating the relationship between electron transfer and pmf.
Shear‐wave splitting and earthquake forecasting
Authors: Gao Yuan , Crampin Stuart
Published: November 2008

Seismic shear‐wave splitting (SWS) monitors the low‐level deformation of fluid‐saturated microcracked rock. We report evidence of systematic SWS changes, recorded above small earthquakes, monitoring the accumulation of stress before earthquakes that allows the time and magnitude of impending large earthquakes to be stress‐forecast. The effects have been seen with hindsight before some 15 earthquakes ranging in magnitude from an M1.7 seismic swarm event in Iceland to the Ms7.7 Chi‐Chi Earthquake in Taiwan, including a successfully stress‐forecast of a M5.0 earthquake in SW Iceland. Characteristic increases in SWS time‐delays are observed before large earthquakes, which abruptly change to deceases shortly before the earthquake occurs. There is a linear relationship between magnitudes and logarithms of durations of both increases and decreases in SWS time‐delays before large impending earthquakes. However, suitably persistent swarms of small earthquakes are too scarce for routine stress‐forecasting. Reliable forecasting requires controlled‐source cross‐hole seismics between neighbouring boreholes in stress‐monitoring sites (SMS). It would be possible to stress‐forecast damaging earthquakes worldwide by a global network of SMS in real time.
Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal
Authors: Brasseur P. , Agnamey P. , Gaye O. , Cisse M. , Badiane M. , Vaillant M. , Taylor W. R. J. , Olliaro P.
Published: November 2008

Objectives  Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria‐endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined.

Methods  Patients with parasitologically confirmed, uncomplicated falciparum malaria were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co‐blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. Target doses were: (i) AS 4 (2–10) mg/kg/day and (ii) AQ 10 (7.5–15) mg/kg/day. Patients receiving therapeutic doses defined dosing accuracy. Treatment‐emergent signs and symptoms (TESS) were recorded.

Results  A total of 3277 patients were treated with loose (n = 1972, weight‐dosed) or co‐blistered (n = 1305, 962 age‐dosed, 343 weight‐dosed) AS + AQ by the research team (n = 966) or clinic staff (n = 2311). AS was dosed correctly in >99% with all regimens. Loose AQ by weight was 98% correct. The co‐blister AQ overdosed 18% of patients when dosed by age and underdosed 13% by weight. Low weight was an independent risk factor for overdosing. The co‐blister had significantly more TESS than the loose product [117/1305 (9%) vs. 41/1972 (2%), relative risk = 4.3 (95% CI: 3.0–6.1, P < 0.0001)]. Age‐based dosing accounted for the difference. TESS occurred mostly within one day (72%) and were mild or moderate (75%).

Conclusion  Artesunate is easier to dose than AQ. Currently available age‐dosed, co‐blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets. It is not the optimal presentation of AS + AQ.
Generalized calcinosis cutis associated with disseminated paecilomycosis in a dog
Authors: Holahan Melissa L. , Loft K. Earl , Swenson Cheryl L. , Martinez‐Ruzafa Ivan
Published: November 2008

A 4‐year‐old spayed female mixed breed dog was referred to the Michigan State University, Veterinary Teaching Hospital (MSU‐VTH) with vomiting, lethargy and anorexia of 2 weeks duration. Abdominal radiographs and ultrasonography showed hepatosplenomegaly. Cytological evaluation of ultrasound‐guided fine needle aspirates of the liver and spleen revealed fungal organisms and pyogranulomatous inflammation; fungal culture documentedPaecilomyces variotiiinfection. The dog received antifungal therapy and supportive care. Multiple firm plaque‐like skin lesions, predominantly involving the inguinal region, developed 18 days after initial presentation and were diagnosed histopathologically as calcinosis cutis. While generalized calcinosis cutis has been reported in three dogs with blastomycosis and one dog with leptospirosis, the association with disseminatedPaecilomycesspp. infection is novel.
The mouse hairy ears mutation exhibits an extended growth (anagen) phase in hair follicles and altered Hoxc gene expression in the ears
Authors: Mentzer Sarah E. , Sundberg John P. , Awgulewitsch Alexander , Chao Hanna H. J. , Carpenter Donald A. , Zhang Wei‐Dong , Rinchik Eugene M. , You Yun
Published: November 2008

The mouse In(15)2Rl (hairy ears, Eh) mutation is a paracentric inversion of the distal half of chromosome 15 (Chr 15). Heterozygous Eh/+ mice display misshaped and hairy ears that have more and longer hair than the ears of their wild‐type littermates. We mapped, cloned and sequenced both inversion breakpoints. No protein‐coding transcript was disrupted by either breakpoint. The proximal breakpoint is located between syntrophin basic 1 (Sntb1) and hyaluronan synthase 2 (Has2), and the distal breakpoint maps between homeobox C4 (Hoxc4) and single‐strand selective monofunctional uracil DNA glycosylase (Smug1), near the middle and the telomere ends of Chr 15, respectively. The inversion spans ~47 megabases. Our genetic analysis suggests that the hairy‐ear phenotype is caused by the proximal breakpoint of the inversion‐bearing Chr 15. Quantitative RNA analysis by real‐time polymerase chain reaction for the genes flanking the breakpoint indicated no changes in expression levels except for some homeobox C (Hoxc) genes whose expression was elevated in developing and mature skin of the ears but not of other body regions. The increased hair length on the ears of Eh/+ mice was due to an extension of the anagen stage in the hair cycle, as determined by histological analysis. Our data indicate that the Eh phenotype arises from mis‐expression of Hoxc genes.
Cytomegalovirusinfection in children who underwent hematopoietic stem cell transplantation at a single center: A retrospective study of the risk factors
Authors: Yoon Hoi Soo , Lee Jae Hee , Choi Eun Soek , Seo Jong Jin , Moon Hyung Nam , Kim Mi‐Na , Im Ho Joon
Published: November 2008

Abstract: CMV infection is one of the major causes of morbidity and mortality after HSCT. The aim of this single center retrospective study was to analyze risk factors for CMV infection in pediatric patients who underwent HSCT. We retrospectively reviewed the medical records of 117 pediatric patients who underwent allogeneic HSCT at Asan Medical Center between December 2000 and January 2007. After HSCT, CMV antigenemia was detected by identifying CMV pp65 early antigen in white blood cells. The incidence of CMV antigenemia was 24% (28/117) at a median of 38 days (range: 19–123 days) after HSCT. In multivariate analysis, CMV antigenemia occurred significantly more often in CMV seropositive recipients, patients who received grafts from alternative donors, T‐cell depleted grafts, patients on ATG‐containing conditioning regimens, or patients who received steroid for acute GVHD (p < 0.05). CMV antigenemia tend to develop earlier in patients who received ATG‐containing conditioning regimens (p = 0.09). A second episode of CMV antigenemia was observed in three out of 28 patients (11%). The incidence of CMV disease was 5.9% (7/117) at a median of 97 days (range: 34–120 days). Manifestation of CMV disease included retinitis in two, pneumonitis in two, hepatitis in one, hepatitis with colitis in one, and gastritis in one. Six of the 12 patients (50%) with HG antigenemia (CMV pp65 antigen positivity ≥40 cells) developed clinical CMV disease, a rate that was significantly higher than seen in patients with LG antigenemia (6.25%; p < 0.01). We recommend that patients with these risk factors should carefully undergo regular evaluations for CMV infection. We also suggest that earlier and more aggressive preemptive treatment and serial follow‐up of CMV disease is necessary in patients with HG‐antigenemia.
Evaluating pharmacokinetics and pharmacodynamics of intravenous busulfan in pediatric patients receiving bone marrow transplantation
Authors: Kim Amy H. , Tse John C. , Ikeda Alan , Moore Theodore B.
Published: November 2008

Abstract:  BU is a commonly used conditioning agent in BMT. However, it is a narrow therapeutic index drug which shows a strong correlation between AUC and both efficacy and toxicity. Studies in pediatric patients have suggested that children less than four yr of age have a greater clearance and thus lower AUC at standard adult doses. The goal of this retrospective analysis was to evaluate any age‐related pharmacokinetic and pharmacodynamic differences in pediatric patients who received BU as a conditioning agent. From 2003 to 2006, 21/77 pediatric patients who received BMT were reviewed. There were 15 males and six females with a mean age of six yr old. Diagnoses of leukemia (n = 11), Hodgkin’s lymphoma (n = 3), myelodysplastic syndrome (n = 2), and other (n = 5) were included. Sixteen patients received BU + cyclophosphamide while five patients received BU + another agent. There were 20 allogeneic and one autologous transplants among which 16 were human leukocyte antigen matched and five were mismatched. Average BU clearance in patients younger than four yr old (n = 8) was 4.1 ± 1.0 mL/min/kg vs. 3.1 ± 0.7 mL/min/kg in patients older than four yr old (n = 13) (p = 0.02). The corresponding averages for AUC were 998 ± 226 μm·min vs. 1155 ± 183 μm·min (p = 0.12). No patients younger than four yr old developed VOD while five of the older patients did (p = 0.044). There were no significant differences in terms of engraftment and acute GvHD. There were significant age‐related pharmacokinetic differences in pediatric patients less than four yr of age receiving BU for conditioning prior to BMT. There was a decrease in drug toxicity seen in these patients.
Preoperative imaging evaluation of the hepatic vasculature in biliary atresia patients undergoing LDLT: Comparison of MDCT and MRI
Authors: Yu Chun‐Yen , Chen Chao‐Long , Huang Tung‐Liang , Chen Tai‐Yi , Tsang Leo Leung‐Chit , Ou Hsin‐You , Concejero Allan M. , Wang Chih‐Chi , Wang Shih‐Ho , Cheng Yu‐Fan
Published: November 2008

Abstract: LT is the definitive treatment option in the management of end‐stage liver disease. Preoperative vascular evaluation plays an important role for a safe and successful operation in LDLT. The purpose of this study is to assess the usefulness and accuracy of CTA and MRA in evaluating vascular anomalies in BA patients undergoing LDLT. Images of CTA and MRA for preoperative vascular evaluation in 57 BA patients undergoing LDLT were reviewed with the operative and pathologic findings. All underwent preoperative CTA and MRA. Pathologic PV (n = 20), interruption of the retro‐hepatic vena cava (n = 1), aberrant right HA from the SMA (n = 2) were confirmed during the transplant operation. The success rate of CTA and MRA in identifying vascular anomalies was 96% and 82%, respectively (p = 0.01). The IQR scores were 3.25 ± 0.53 for CTA and 2.91 ± 0.70 for MRA (p = 0.001). The sensitivity, specificity and accuracy of CTA were 85%, 97% and 93%, respectively; and for MRA, were 65%, 95% and 84%, respectively. CTA is superior than MRA in the preoperative evaluation of the vascular anatomy in pediatric BA LDLT candidates.
Purification, cDNA cloning and functional expression of NADPH‐cytochrome P450 reductase from Centaurium erythraea cell cultures
Authors: Schwarz H. , Liu B. , Peters S. , Barillas W. , Beerhues L.
Published: November 2008

Solubilised NADPH‐cytochrome P450 reductase (CPR) was purified from the microsomal fraction of centaury (Centaurium erythraea) cell cultures by Q‐anion exchange chromatography and affinity chromatography on adenosine 2′,5′‐diphosphate agarose. SDS‐PAGE demonstrated the presence of three CPR isoforms with molecular masses of 77, 79 and 81 kDa. The 79‐ and 81‐kDa isoforms were identified as glycoproteins when blotted following SDS‐PAGE and subjected to a sugar detection procedure. A homology‐based approach led to the isolation of a CPR cDNA encoding the 77‐kDa isoform. The enzyme was a class I CPR, possessing a short N‐terminus upstream of the membrane anchor. The amino acid sequence contained a putative N‐glycosylation site, indicating that the two major isoforms of 77 and 79 kDa are related through attachment of an oligosaccharide chain. This glycosylation process was also found upon heterologous expression in yeast. When co‐expressed in yeast together with centaury coniferyl alcohol 5‐hydroxylase, CPR efficiently supported the activity of the P450 enzyme. The genome of C. erythraea was found to contain a second CPR gene. RT‐PCR experiments using gene‐specific primers revealed differential regulation of the two CPR genes. While CPR 2 mRNA was strongly induced by the addition of methyl jasmonate to the cell cultures, the CPR 1 expression level did not change after this elicitation.