bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutant Huntingtin Impairs Post-Golgi Trafficking to Lysosomes by Delocalizing Optineurin/Rab8 Complex from the Golgi Apparatus
Authors: del Toro Daniel , Alberch Jordi , Lázaro-Diéguez Francisco , Martín-Ibáñez Raquel , Xifró Xavier , Egea Gustavo , Canals Josep M.
Published: January 2009

Huntingtin regulates post-Golgi trafficking of secreted proteins. Here, we studied the mechanism by which mutant huntingtin impairs this process. Colocalization studies and Western blot analysis of isolated Golgi membranes showed a reduction of huntingtin in the Golgi apparatus of cells expressing mutant huntingtin. These findings correlated with a decrease in the levels of optineurin and Rab8 in the Golgi apparatus that can be reverted by overexpression of full-length wild-type huntingtin. In addition, immunoprecipitation studies showed reduced interaction between mutant huntingtin and optineurin/Rab8. Cells expressing mutant huntingtin produced both an accumulation of clathrin adaptor complex 1 at the Golgi and an increase of clathrin-coated vesicles in the vicinity of Golgi cisternae as revealed by electron microscopy. Furthermore, inverse fluorescence recovery after photobleaching analysis for lysosomal-associated membrane protein-1 and mannose-6-phosphate receptor showed that the optineurin/Rab8-dependent post-Golgi trafficking to lysosomes was impaired in cells expressing mutant huntingtin or reducing huntingtin levels by small interfering RNA. Accordingly, these cells showed a lower content of cathepsin D in lysosomes, which led to an overall reduction of lysosomal activity. Together, our results indicate that mutant huntingtin perturbs post-Golgi trafficking to lysosomal compartments by delocalizing the optineurin/Rab8 complex, which, in turn, affects the lysosomal function.
The Insulin/Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid
Authors: Lee Han-Kyu , Kumar Pravir , Fu Qinghao , Rosen Kenneth M. , Querfurth Henry W.
Published: January 2009

Intraneuronal β-amyloid (Aβi) accumulates early in Alzheimer's disease (AD) and inclusion body myositis. Several organelles, receptor molecules, homeostatic processes, and signal transduction components have been identified as sensitive to Aβ. Although prior studies implicate the insulin-PI3K-Akt signaling cascade, a specific step within this or any essential metabolic or survival pathway has not emerged as a molecular target. We tested the effect of Aβ42 on each component of this cascade. In AD brain, the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control. In cell culture, Aβiexpression inhibited both insulin-induced Akt phosphorylation and activity. In vitro experiments identified that β-amyloid (Aβ), especially oligomer preparations, specifically interrupted the PDK-dependent activation of Akt. Aβialso blocked the association between PDK and Akt in cell-based and in vitro experiments. Importantly, Aβ did not interrupt Akt or PI3K activities (once stimulated) nor did it affect more proximal signal events. These results offer a novel therapeutic strategy to neutralize Aβ-induced energy failure and neuronal death.
Association of v-ErbA with Smad4 Disrupts TGF-β Signaling
Authors: Erickson Richard A. , Liu Xuedong
Published: January 2009

Disruption of the transforming growth factor-β (TGF-β) pathway is observed in the majority of cancers. To further understand TGF-β pathway inactivation in cancer, we stably expressed the v-ErbA oncoprotein in TGF-β responsive cells. v-ErbA participates in erythroleukemic transformation of cells induced by the avian erythroblastosis virus (AEV). Here we demonstrate that expression of v-ErbA was sufficient to antagonize TGF-β–induced cell growth inhibition and that dysregulation of TGF-β signaling required that v-ErbA associate with the Smad4 which sequesters Smad4 in the cytoplasm. We also show that AEV-transformed erythroleukemia cells were resistant to TGF-β–induced growth inhibition and that TGF-β sensitivity could be recovered by reducing v-ErbA expression. Our results reveal a novel mechanism for oncogenic disruption of TGF-β signaling and provide a mechanistic explanation of v-ErbA activity in AEV-induced erythroleukemia.
Palmitoylation of Cytoskeleton Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling
Authors: Planey Sonia L. , Keay Susan K. , Zhang Chen-Ou , Zacharias David A.
Published: January 2009

Previously, we identified cytoskeleton-associated protein 4 (CKAP4) as a major substrate of the palmitoyl acyltransferase, DHHC2, using a novel proteomic method called palmitoyl-cysteine identification, capture and analysis (PICA). CKAP4 is a reversibly palmitoylated and phosphorylated protein that links the ER to the cytoskeleton. It is also a high-affinity receptor for antiproliferative factor (APF), a small sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). The role of DHHC2-mediated palmitoylation of CKAP4 in the antiproliferative response of HeLa and normal bladder epithelial cells to APF was investigated. Our data show that siRNA-mediated knockdown of DHHC2 and consequent suppression of CKAP4 palmitoylation inhibited the ability of APF to regulate cellular proliferation and blocked APF-induced changes in the expression of E-cadherin, vimentin, and ZO-1 (genes known to play a role in cellular proliferation and tumorigenesis). Immunocytochemistry revealed that CKAP4 palmitoylation by DHHC2 is required for its trafficking from the ER to the plasma membrane and for its nuclear localization. These data suggest an important role for DHHC2-mediated palmitoylation of CKAP4 in IC and in opposing cancer-related cellular behaviors and support the idea that DHHC2 is a tumor suppressor.
Mitotic Exit in the Absence of Separase Activity
Authors: Lu Ying , Cross Frederick
Published: January 2009

In budding yeast, three interdigitated pathways regulate mitotic exit (ME): mitotic cyclin–cyclin-dependent kinase (Cdk) inactivation; the Cdc14 early anaphase release (FEAR) network, including a nonproteolytic function of separase (Esp1); and the mitotic exit network (MEN) driven by interaction between the spindle pole body and the bud cortex. Here, we evaluate the contributions of these pathways to ME kinetics. Reducing Cdk activity is critical for ME, and the MEN contributes strongly to ME efficiency. Esp1 contributes to ME kinetics mainly through cohesin cleavage: the Esp1 requirement can be largely bypassed if cells are provided Esp1-independent means of separating sister chromatids. In the absence of Esp1 activity, we observed only a minor ME delay consistent with a FEAR defect. Esp1 overexpression drives ME in Cdc20-depleted cells arrested in metaphase. We have found that this activity of overexpressed Esp1 depended on spindle integrity and the MEN. We defined the first quantitative measure for Cdc14 release based on colocalization with the Net1 nucleolar anchor. This measure indicates efficient Cdc14 release upon MEN activation; release driven by Esp1 in the absence of microtubules was inefficient and incapable of driving ME. We also found a novel role for the MEN: activating Cdc14 nuclear export, even in the absence of Net1.
“Making Connections”: Insights into Relationship Marketing from the Australasian Stock and Station Agent Industry
Authors: Ville Simon
Published: January 2009

Relationship marketing has received little attention from business historians who have favored the study of branding, associational advertising, market research, and the role of marketing agencies, particularly in relation to modern consumer manufacturing. Although the term relationship marketing is of recent origin, we analyze its practice under a different guise, “connections,” over several centuries: we draw on the extensive archival evidence of a rural business services industry in Australia and New Zealand. Relationship marketing's emphasis upon close and enduring individual customer relationships mitigated uncertainty of performance and behaviour, on both sides of the transaction, created by a long and geographically extended supply chain. The success of these relationships contributed to the primary industry-led economic development of both nations.
Evidence for the Construction of Quires in a Fifteenth-Century English Manuscript
Authors: Wakelin Daniel , Burlinson Christopher
Published: January 2009

Recent conservation work on St John’s College, Cambridge, MS S.54, a late-fifteenth-century collection of Middle English carols and lyrics, uncovered connecting ‘bolts’ showing that what had seemed to be separate bifolia were in fact quadrifolia, with further evidence suggesting that the quadrifolia derived from octofolia, or pages created by folding sheets three times and only then cutting them apart. These are the only recorded surviving ‘bolts’ in a manuscript in English, and they offer further evidence for the importance of folding in the construction of quires. The use of folded sheets, cut open at a late stage, also tells us much about the transmission and circulation of the Middle English carols and lyrics in this manuscript.
Fecal β‐Defensin‐2 in Children With Inflammatory Bowel Diseases
Authors: Kapel Nathalie , Benahmed Nacer , Morali Alain , Svahn Johan , Canioni Danielle , Goulet Olivier , Ruemmele Frank M
Published: January 2009

Defensins, endogenous antibiotic peptides, are part of the intestinal epithelial barrier. In this pilot study we analyzed the possibility of measuring fecal β‐defensin‐2 (HBD2) in comparing inflammatory and noninflammatory conditions. In samples from healthy control individuals, low levels of HBD2 were detectable, which markedly rose under inflammatory conditions (P = 0.0002 vs normal control individuals), the highest levels being observed in patients with ulcerative colitis (median 356 ng/g, range 40–527). Despite frank inflammation, Crohn disease patients with colitis had significantly lower, albeit enhanced, HBD2 levels than did ulcerative colitis patients. These data confirm the possibility of quantifying HBD2 in feces and indicate that colitis in Crohn disease and colitis in ulcerative colitis differ from each other with respect to their ability to secrete HBD2.
Role of the Multichannel Intraluminal Impedance Technique in Infants and Children
Authors: van Wijk Michiel P , Benninga Marc A , Omari Taher I
Published: January 2009

Recently, multichannel intraluminal impedance (MII) was added to the repertoire of tests available to study esophageal (patho)physiology in children. MII has since been used in 2 major areas. First, it has been used as a diagnostic test for gastroesophageal reflux disease (GERD). The main advantage over traditional pH monitoring is its ability to detect both acid and nonacid gastroesophageal reflux (GER) and to discern between liquid and gas GER.

Although feasible with multiple pH sensors, the MII technique routinely detects the proximal extent of a GER episode. When a pH sensor is added to the MII‐catheter, important information about the acidity of a GER event can be gathered.

The second area in which the role of MII has been investigated is that of esophageal function testing. Manometry classically reveals information about esophageal pressure patterns and sphincter function, but does not inform us about bolus flow. MII not only detects the presence of esophageal flow but also adds information on the direction of flow, duration of bolus presence, completeness of bolus clearance, and composition of a bolus.

The combination of MII with manometry enables determination of the relationship between esophageal pressures and flow and, therefore, enhances evaluation of esophageal function in terms of assessment of mechanisms of esophageal volume clearance. In addition, this technique will improve our understanding of (patho)physiological mechanisms in pediatric GERD and other esophageal motility disorders.
LTP in hippocampal area CA1 is induced by burst stimulation over a broad frequency range centered around delta
Authors: Grover Lawrence M. , Kim Eunyoung , Cooke Jennifer D. , Holmes William R.
Published: January 2009

Long-term potentiation (LTP) is typically studied using either continuous high-frequency stimulation or theta burst stimulation. Previous studies emphasized the physiological relevance of theta frequency; however, synchronized hippocampal activity occurs over a broader frequency range. We therefore tested burst stimulation at intervals from 100 msec to 20 sec (10 Hz to 0.05 Hz). LTP at Schaffer collateral–CA1 synapses was obtained at intervals from 100 msec to 5 sec, with maximal LTP at 350–500 msec (2–3 Hz, delta frequency). In addition, a short-duration potentiation was present over the entire range of burst intervals. We found that N-methyl-d-aspartic acid (NMDA) receptors were more important for LTP induction by burst stimulation, but L-type calcium channels were more important for LTP induction by continuous high-frequency stimulation. NMDA receptors were even more critical for short-duration potentiation than they were for LTP. We also compared repeated burst stimulation with a single primed burst. In contrast to results from repeated burst stimulation, primed burst potentiation was greater when a 200-msec interval (theta frequency) was used, and a 500-msec interval was ineffective. Whole-cell recordings of postsynaptic membrane potential during burst stimulation revealed two factors that may determine the interval dependence of LTP. First, excitatory postsynaptic potentials facilitated across bursts at 500-msec intervals but not 200-msec or 1-sec intervals. Second, synaptic inhibition was suppressed by burst stimulation at intervals between 200 msec and 1 sec. Our data show that CA1 synapses are more broadly tuned for potentiation than previously appreciated.
Polycapillary-optics-based micro-XANES and micro-EXAFS at a third-generation bending-magnet beamline
Authors: Silversmit Geert , Vekemans Bart , Nikitenko Sergey , Bras Wim , Czhech Viktoria , Zaray Gyula , Szaloki Imre , Vincze Laszlo
Published: January 2009

A focusing system based on a polycapillary half-lens optic has been successfully tested for transmission and fluorescence µ-X-ray absorption spectroscopy at a third-generation bending-magnet beamline equipped with a non-fixed-exit Si(111) monochromator. The vertical positional variations of the X-ray beam owing to the use of a non-fixed-exit monochromator were shown to pose only a limited problem by using the polycapillary optic. The expected height variation for an EXAFS scan around the Fe K-edge is approximately 200 µm on the lens input side and this was reduced to ∼1 µm for the focused beam. Beam sizes (FWHM) of 12–16 µm, transmission efficiencies of 25–45% and intensity gain factors, compared with the non-focused beam, of about 2000 were obtained in the 7–14 keV energy range for an incoming beam of 0.5 × 2 mm (vertical × horizontal). As a practical application, an As K-edge µ-XANES study of cucumber root and hypocotyl was performed to determine the As oxidation state in the different plant parts and to identify a possible metabolic conversion by the plant.
Generation of drug‐resistant mutants of Helicobacter pylori in the presence of peroxynitrite, a derivative of nitric oxide, at pathophysiological concentration
Authors: Kuwahara Hideo , Kariu Tohru , Fang Jun , Maeda Hiroshi
Published: January 2009

In the present study it has been shown that the reactive nitrogen species, peroxynitrite, can cause at least a 7.1‐fold increase in the frequency of occurrence of drug‐resistant mutants of Helicobacter pylori at a pathophysiological concentration (e.g. 1.0 μM) and in the presence of CLR. Furthermore, the CLR MIC of these resistant H. pylori strains increased by at least 250 times or higher in CLR susceptibility. In the 45 resistant strains, the modification of 23S rRNA A2142G was the predominant mutation (22/45), followed by A2143G (17/45) within the sequences of 23S rRNA. The other mutants were one each (1/45) in A2142T, and T2269G, and two each (2/45) in C2695G and T1944C, respectively. These results show that the inflammatory host reaction involving induction of reactive oxygen species (e.g. O·−2), and the inducible form of nitric oxide synthase, is a significant cause of mutation via peroxynitrite formation, particularly in drug‐resistant bacterial strains.
An international survey of training programs for treating tobacco dependence
Authors: Rigotti Nancy A. , Bitton Asaf , Richards Ann E. , Reyen Michele , Wassum Kenneth , Raw Martin
Published: January 2009

Aims  The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) requires countries to implement tobacco dependence treatment programs. To provide treatment effectively, a country needs trained individuals to deliver these services. We report on the global status of programs that train individuals to provide tobacco dependence treatment.

Design  Cross‐sectional web‐based survey of tobacco treatment training programs in a stratified convenience sample of countries chosen to vary by WHO geographic region and World Bank income level.

Participants  Key informants in 48 countries; 70% of 69 countries who were sent surveys responded.

Measurements  Program prevalence, frequency, duration and size; background of trainees; content (adherence to pre‐defined core competencies); funding sources; challenges.

Findings  We identified 61 current tobacco treatment training programs in 37 (77%) of 48 countries responding to the survey. Three‐quarters of them began in 2000 or later, and 40% began after 2003, when the FCTC was adopted. Programs estimated training 14 194 individuals in 2007. Training was offered to a variety of professionals and paraprofessionals, but most often to physicians and nurses. Median program duration was 16 hours, but programs' duration, intensity and size varied widely. Most programs used evidence‐based guidelines and reported adherence to core tobacco treatment competencies. Training programs were less frequent in low‐income countries and in Africa. Securing funding was the major challenge for most programs; current funding sources were government (58%), non‐government organizations (23%), pharmaceutical companies (17%) and, in one case, the tobacco industry.

Conclusion  Training programs for tobacco treatment providers are diverse and growing. Most upper‐ and middle‐income countries have programs, and most programs appear to be evidence‐based. However, funding is a major challenge. In particular, more programs are needed for non‐physicians and for low‐income countries.
Cost‐effectiveness of pharmacy and group behavioural support smoking cessation services in Glasgow
Authors: Boyd Kathleen A. , Briggs Andrew H.
Published: January 2009

Aims  Smokers attending group‐based support for smoking cessation in Glasgow are significantly more likely to be successful than those attending pharmacy‐based support. This study examined the cost‐effectiveness of these two modes of support.

Design  Combination of observational study data and information from National Health Service (NHS) Greater Glasgow and Clyde smoking cessation services.

Setting  Glasgow, Scotland.

Participants  A total of 1979 smokers who accessed either of the cessation services between March and May 2007.

Intervention  Two smoking treatment services offering one‐to‐one support in pharmacies, and providing group counselling in the community.

Measurements  Routine monitoring data on resource use and smoking status (carbon monoxide‐validated, self‐reported, non‐quitters and relapsers) at 4‐week follow‐up.

Findings  The incremental cost per 4‐week quitter for pharmacy support was found to be approximately £772, and £1612 for group support, in comparison to self‐quit cessation attempts. These findings compare favourably with previously published outcomes from cost‐effectiveness smoking cessation studies. Assuming a relapse rate of 75% from 4 weeks to 1 year and a further 35% beyond 1 year, and combining this with an average of 1.98 quality adjusted life years (QALY) gained per permanent cessation, provides an estimated incremental cost per QALY of £4400 for the pharmacy service and £5400 for group support service.

Conclusions  Group support and pharmacy‐based support for smoking cessation are both extremely cost‐effective.
Bortezomib, low‐dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma
Authors: Popat Rakesh , Oakervee Heather , Williams Catherine , Cook Mark , Craddock Charles , Basu Supratik , Singer Charles , Harding Stephen , Foot Nicola , Hallam Simon , Odeh Liz , Joel Simon , Cavenagh Jamie
Published: January 2009

This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2·5–10·0 mg/m2) on day 2 of a 28‐day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty‐three patients were enrolled. The MTD was defined at melphalan 7·5 mg/m2 and bortezomib 1·3 mg/m2. The overall response rate (ORR) was 68% (23% complete or near‐complete responses [CR/nCR]) whilst at the MTD (n = 33) the ORR was 76% (34% CR/nCR). After median follow‐up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD (P < 0·05 vs. non‐MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low‐dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.
Responses of dryland soil respiration and soil carbon pool size to abrupt vs. gradual and individual vs. combined changes in soil temperature, precipitation, and atmospheric [CO2]: a simulation analysis
Authors: SHEN WEIJUN , REYNOLDS JAMES F. , HUI DAFENG
Published: January 2009

With the large extent and great amount of soil carbon (C) storage, drylands play an important role in terrestrial C balance and feedbacks to climate change. Yet, how dryland soils respond to gradual and concomitant changes in multiple global change drivers [e.g., temperature (Ts), precipitation (Ppt), and atmospheric [CO2] (CO2)] has rarely been studied. We used a process‐based ecosystem model patch arid land simulator to simulate dryland soil respiration (Rs) and C pool size (Cs) changes to abrupt vs. gradual and single vs. combined alterations in Ts, Ppt and CO2 at multiple treatment levels. Results showed that abrupt perturbations generally resulted in larger Rs and had longer differentiated impacts than did gradual perturbations. Rs was stimulated by increases in Ts, Ppt, and CO2 in a nonlinear fashion (e.g., parabolically or asymptotically) but suppressed by Ppt reduction. Warming mainly stimulated heterotrophic Rs (i.e., Rh) whereas Ppt and CO2 influenced autotrophic Rs (i.e., Ra). The combined effects of warming, Ppt, and CO2 were nonadditive of primary single‐factor effects as a result of substantial interactions among these factors. Warming amplified the effects of both Ppt addition and CO2 elevation whereas Ppt addition and CO2 elevation counteracted with each other. Precipitation reduction either magnified or suppressed warming and CO2 effects, depending on the magnitude of factor's alteration and the components of Rs (Ra or Rh) being examined. Overall, Ppt had dominant influence on dryland Rs and Cs over Ts and CO2. Increasing Ppt individually or in combination with Ts and CO2 benefited soil C sequestration. We therefore suggested that global change experimental studies for dryland ecosystems should focus more on the effects of precipitation regime changes and the combined effects of Ppt with other global change factors (e.g., Ts, CO2, and N deposition).
Predicting impacts of climate‐induced range expansion: an experimental framework and a test involving key grazers on temperate rocky shores
Authors: FIRTH LOUISE B. , CROWE TASMAN P. , MOORE PIPPA , THOMPSON RICHARD C. , HAWKINS STEPHEN J.
Published: January 2009

Climate change has strong potential to modify the structure and functioning of ecosystems, but experimental field studies into its effects are rare. On rocky shores, grazing limpets strongly affect ecosystem structure and their distribution in NW Europe is changing in response to climate change. Three limpet species co‐occur in SW Britain (Patella vulgata, Patella ulyssiponensisandPatella depressa) on open rock and in pools. Shores in Ireland are similar, but currently lackP. depressa. It is anticipated thatP. depressawill expand its range into Ireland as the climate warms, but we currently lack an empirical basis to predict the consequences of this change. Recent studies show that increasing abundance ofP. depressaon British shores has been accompanied by a decline ofP. vulgatasuggesting interspecific competition. In this study, a new experimental framework was used to examine the potential forP. depressato affectP. vulgataon Irish shores.P. vulgatawas experimentally transplanted into enclosures on open rock and in pools in both Ireland and Britain. In pools, treatments also included transplantedP. ulyssiponensisto mimic natural assemblages. Growth and mortality ofP. vulgatawere measured over 6 months with no differences between Ireland and Britain. In Britain,P. vulgatacaged in pools with transplantedP. depressaandP. ulyssiponensisshowed reduced growth, compared with when caged in pools withP. ulyssiponensisalone. There was no effect ofP. depressaon the growth rate ofP. vulgataon open rock. Results indicate that if the range ofP. depressaextends into Ireland, it would reduce the growth ofP. vulgatawhere it co‐occurs withP. ulyssiponensisin pools. The framework used here provides a field‐based approach that could be used to examine the impacts of climate‐induced range expansions on the structure and functioning of other ecosystems.
Assessing the effect of elevated carbon dioxide on soil carbon: a comparison of four meta‐analyses
Authors: HUNGATE BRUCE A. , Van GROENIGEN KEES‐JAN , SIX JOHAN , JASTROW JULIE D. , LUO YIQI , De GRAAFF MARIE‐ANNE , Van KESSEL CHRIS , OSENBERG CRAIG W.
Published: January 2009

Soil is the largest reservoir of organic carbon (C) in the terrestrial biosphere and soil C has a relatively long mean residence time. Rising atmospheric carbon dioxide (CO2) concentrations generally increase plant growth and C input to soil, suggesting that soil might help mitigate atmospheric CO2 rise and global warming. But to what extent mitigation will occur is unclear. The large size of the soil C pool not only makes it a potential buffer against rising atmospheric CO2, but also makes it difficult to measure changes amid the existing background. Meta‐analysis is one tool that can overcome the limited power of single studies. Four recent meta‐analyses addressed this issue but reached somewhat different conclusions about the effect of elevated CO2 on soil C accumulation, especially regarding the role of nitrogen (N) inputs. Here, we assess the extent of differences between these conclusions and propose a new analysis of the data. The four meta‐analyses included different studies, derived different effect size estimates from common studies, used different weighting functions and metrics of effect size, and used different approaches to address nonindependence of effect sizes. Although all factors influenced the mean effect size estimates and subsequent inferences, the approach to independence had the largest influence. We recommend that meta‐analysts critically assess and report choices about effect size metrics and weighting functions, and criteria for study selection and independence. Such decisions need to be justified carefully because they affect the basis for inference. Our new analysis, with a combined data set, confirms that the effect of elevated CO2 on net soil C accumulation increases with the addition of N fertilizers. Although the effect at low N inputs was not significant, statistical power to detect biogeochemically important effect sizes at low N is limited, even with meta‐analysis, suggesting the continued need for long‐term experiments.
Regional water resource implications of bioethanol production in the Southeastern United States
Authors: EVANS JASON M. , COHEN MATTHEW J.
Published: January 2009

The Energy Independence and Security Act (EISA) of 2007 mandates US production of 136 billion L of biofuel by 2022. This target implies an appropriation of regional primary production for dedicated feedstocks at scales that may dramatically affect water supply, exacerbate existing water quality challenges, and force undesirable environmental resource trade offs. Using a comparative life cycle approach, we assess energy balances and water resource implications for four dedicated ethanol feedstocks – corn, sugarcane, sweet sorghum, and southern pine – in two southeastern states, Florida and Georgia, which are a presumed epicenter for future biofuel production. Net energy benefit ratios for ethanol and coproducts range were 1.26 for corn, 1.94 for sweet sorghum, 2.51 for sugarcane, and 2.97 for southern pine. Corn also has high nitrogen (N) and water demand (11.2 kg GJnet−1 and 188 m3 GJnet−1, respectively) compared with other feedstocks, making it a poor choice for regional ethanol production. Southern pine, in contrast, has relatively low N demand (0.4 kg GJnet−1) and negligible irrigation needs. However, it has comparatively low gross productivity, which results in large land area per unit ethanol production (208 m2 GJnet−1), and, by association, substantial indirect and incremental water use (51 m3 GJnet−1). Ultimately, all four feedstocks require substantial land (10.1, 3.1, 2.5, and 6.1 million ha for corn, sugarcane, sweet sorghum, and pine, respectively), annual N fertilization (3230, 574, 396, 109 million kg N) and annual total water (54 400, 20 840, 8840, and 14 970 million m3) resources when scaled up to meet EISA renewable fuel standards production goals. This production would, in turn, offset only 17.5% of regional gasoline consumption on a gross basis, and substantially less when evaluated on a net basis. Utilization of existing waste biomass sources may ameliorate these effects, but does not obviate the need for dedicated primary feedstock production. Careful scrutiny of environmental trade‐offs is necessary before embracing aggressive ethanol production mandates.
Oral and general health‐related quality of life among young patients with haemophilia
Authors: ALPKILIÇ BASKIRT E. , AK G. , ZULFIKAR B.
Published: January 2009

Summary.  The clinical diagnosis of dental diseases may indicate their cause and prognosis, however it gives little information about resulting levels of impairment from the patients’ perspective. In this study, we aimed to investigate oral and general health‐related quality of life (OHRQoL‐HRQoL) in patients with haemophilia; and to test whether haemophiliacs would have worse or better OHRQoL compared with the general population. Data were collected from haemophiliacs (age range 14–35; mean 23 ± 6.58, n = 71) and age/sex‐matched controls (age range 14–35; mean 21.00 ± 6.45, n = 60) through face‐to‐face interviews including nine questions and using oral health impact profile (OHIP)‐14, oral health‐related quality of life‐UK (OHQoL‐UK), short‐form general measure of health (SF)‐36 to measure self‐rating oral health status, perceived dental treatment needs, tooth brushing frequencies, OHRQoL‐HRQoL. In the field of self‐rating oral health status, perceived dental treatment needs, tooth brushing frequencies and OHIP, OHQoL‐UK, SF‐36 scores – except the subscales including vitality, role emotional and mental health – the control group is in better conditions compared with the haemophilia group. At the same time, both the two groups are in good conditions in dental attendance, vitality, role emotional and mental health. Life quality is related with the perceived discrepancy between the reality of what a person has and the concept of what that person wants, needs or expects. In order to eliminate the dilemma in the field of health, we should facilitate the haemophiliacs’ lives by serving the health care in a multidisciplinary view.
Care dependency of hospitalized children: testing the Care Dependency Scale for Paediatrics in a cross‐cultural comparison
Authors: Tork Hanan , Dassen Theo , Lohrmann Christa
Published: January 2009

Title.  Care dependency of hospitalized children: testing the Care Dependency Scale for Paediatrics in a cross‐cultural comparison.

Aim.  This paper is a report of a study to examine the psychometric properties of the Care Dependency Scale for Paediatrics in Germany and Egypt and to compare the care dependency of school‐age children in both countries.

Background.  Cross‐cultural differences in care dependency of older adults have been documented in the literature, but little is known about the differences and similarities with regard to children’s care dependency in different cultures.

Method.  A convenience sample of 258 school‐aged children from Germany and Egypt participated in the study in 2005. The reliability of the Care Dependency Scale for Paediatrics was assessed in terms of internal consistency and interrater reliability. Factor analysis (principal component analysis) was employed to verify the construct validity. A Visual Analogue Scale was used to investigate the criterion‐related validity.

Findings.  Good internal consistency was detected both for the Arabic and German versions. Factor analysis revealed one factor for both versions. A Pearson’s correlation between the Care Dependency Scale for Paediatrics and Visual Analogue Scale was statistically significant for both versions indicating criterion‐related validity. Statistically significant differences between the participants were detected regarding the mean sum score on the Care Dependency Scale for Paediatrics.

Conclusion.  The Care Dependency Scale for Paediatrics is a reliable and valid tool for assessing the care dependency of children and is recommended for assessing the care dependency of children from different ethnic origins. Differences in care dependency between German and Egyptian children were detected, which might be due to cultural differences.
Innovative behaviour: the effect of structural and psychological empowerment on nurses
Authors: Knol Jeannette , Van Linge Roland
Published: January 2009

Title. Innovative behaviour: the effect of structural and psychological empowerment on nurses.

Aim. This paper is a report of a study to investigate the relationship between structural empowerment/psychological empowerment and innovative behaviour.

Background. Innovative behaviour is essential for nurses in today’s dynamic healthcare systems. Empowerment has become an increasingly important factor in predicting innovative behaviour. Structural empowerment refers to power based on the employee’s position in the organization, while psychological empowerment consists of the fundamental personal convictions that employees have about their role in the organization.

Methods. A cross‐sectional correlational survey was conducted in the Netherlands in 2007 with 519 Registered Nurses. The instruments used were the Conditions of Work Effectiveness Questionnaire II, the Psychological Empowerment Instrument and the Questionnaire Innovative Behaviour. Four hypotheses were tested using descriptive statistics, bivariate and multiple regression and one‐way analysis of variance.

Results. Structural and psychological empowerment were statistically significant predictors of innovative behaviour. Informal power and impact were the most relevant determinants of innovative behaviour, the latter the strongest. Psychological empowerment functioned as a mediator between structural empowerment and innovative behaviour. The expected moderating effect of structural empowerment was not proven.

Conclusion. Organizations need to create the right conditions to be able to strengthen nurses’ empowerment. Networking is an important skill which should be incorporated in the nursing education. Future research should take into consideration nursing culture and personality traits as determining factors. Replication of this study in another setting and a study examining causality are recommended so that additional empirical evidence may be obtained.
Surviving a life‐threatening crisis: Taiwan’s nurse leaders’ reflections and difficulties fighting the SARS epidemic
Authors: Shih Fu‐Jin , Turale Sue , Lin Yaw‐Sheng , Gau Meei‐Ling , Kao Ching‐Chiu , Yang Chyn‐Yng , Liao Yen‐Chi
Published: January 2009

Aim.  This study explored Taiwan’s nurse leaders’ reflections and experiences of the difficulties they encountered and survival strategies they employed fighting the severe acute respiratory syndrome epidemic and the background context framing these phenomena.

Background.  On several continents in 2002–2003, the highly infectious severe acute respiratory syndrome overwhelmed health care systems and health professionals who had to provide care in situations involving high personal risk and stress, some becoming infected and dying. Nurse leaders in Taiwan had to develop new strategies and support systems for nursing care.

Design.  A two‐step within‐method qualitative triangulation research design.

Methods.  Focus group in‐depth interviews held with 70 nurse leaders from four Northern Taiwan hospitals involved in the severe acute respiratory syndrome epidemic. Participants then completed an open ended questionnaire. Content analysis was undertaken with data and stages and themes generated. Data were then analysed using Hobfall’s concepts of conservation of resources to further discuss participants’ reactions and actions in the severe acute respiratory syndrome crisis.

Results.  Participants worked under incredible stress to lead the profession through a period of crisis. Five stages arose in the participants’ involvement against severe acute respiratory syndrome over 12 weeks: facing shock and chaos; searching for reliable sources to clarify myths; developing and adjusting nursing care; supporting nurses and their clients; and rewarding nurses.

Conclusion.  Nurse leaders become important executors of intervention in this health disaster, requiring emotional intelligence to manage their internal conflicts and interpersonal relationships effectively. They developed sociopolitical and analytical abilities and crucial requirements for planning and implementing strategies in areas where none previously existed. Building support systems was an important resource for managing conflicts between familial and professional roles.

Relevance to clinical practice.  Findings will assist nurse leaders to prepare themselves and the profession to better deal with disaster management in similar infectious outbreaks in the future.
Use of high‐pressure freeze fixation and freeze fracture electron microscopy to study the influence of the phospholipid molar ratio in the morphology and alignment of bicelles
Authors: BARBOSA‐BARROS L. , MAZA A. DE LA , WALTHER P. , LINARES A.M. , FELIZ M. , ESTELRICH J. , LÓPEZ OLGA
Published: January 2009

The high‐pressure freeze fixation and freeze fracture electron microscopy techniques were combined with the 31P nuclear magnetic resonance to study the morphological transitions of two different dimyristoyl‐phosphatidilcholine/dihexanoyl‐phosphocholine aggregates by the effect of temperature. Through these techniques, the relationship between magnetic alignment and the morphology of alignable and non‐alignable aggregates was evaluated. The micrographs related to the non‐alignable dimyristoyl‐phosphatidilcholine/dihexanoyl‐phosphocholine sample presented rounded objects at a temperature below the dimyristoyl‐phosphatidilcholine phase transition (Tm) and, above this temperature an increase of viscosity was followed by the appearance of large elongated aggregates. The micrographs related to the alignable dimyristoyl‐phosphatidilcholine/dihexanoyl‐phosphocholine sample presented discoidal objects below Tm. Above Tm, when the best alignment was achieved, the images showed large areas of lamellar stacked bilayers and the presence of some multilamellar vesicles. Our results reveal that the composition of the aggregates is a key factor determining the morphological transitions of the bicellar systems. Understanding of the rules governing these transitions is crucial to modulate characteristics of these systems and to adequate them for different applications.
XuvTools: free, fast and reliable stitching of large 3D datasets
Authors: EMMENLAUER M. , RONNEBERGER O. , PONTI A. , SCHWARB P. , GRIFFA A. , FILIPPI A. , NITSCHKE R. , DRIEVER W. , BURKHARDT H.
Published: January 2009

Current biomedical research increasingly requires imaging large and thick 3D structures at high resolution. Prominent examples are the tracking of fine filaments over long distances in brain slices, or the localization of gene expression or cell migration in whole animals like Caenorhabditis elegans or zebrafish. To obtain both high resolution and a large field of view (FOV), a combination of multiple recordings (‘tiles’) is one of the options. Although hardware solutions exist for fast and reproducible acquisition of multiple 3D tiles, generic software solutions are missing to assemble (‘stitch’) these tiles quickly and accurately.

In this paper, we present a framework that achieves fully automated recombination of tiles recorded at arbitrary positions in 3D space, as long as some small overlap between tiles is provided. A fully automated 3D correlation between all tiles is achieved such that no manual interaction or prior knowledge about tile positions is needed. We use (1) phase‐only correlation in a multi‐scale approach to estimate the coarse positions, (2) normalized cross‐correlation of small patches extracted at salient points to obtain the precise matches, (3) find the globally optimal placement for all tiles by a singular value decomposition and (4) accomplish a nearly seamless stitching by a bleaching correction at the tile borders. If the dataset contains multiple channels, all channels are used to obtain the best matches between tiles. For speedup we employ a heuristic method to prune unneeded correlations, and compute all correlations via the fast Fourier transform (FFT), thereby achieving very good runtime performance.

We demonstrate the successful application of the proposed framework to a wide range of different datasets from whole zebrafish embryos and C. elegans, mouse and rat brain slices and fine plant hairs (trichome). Further, we compare our stitching results to those of other commercially and freely available software solutions.

The algorithms presented are being made available freely as an open source toolset ‘XuvTools’ at the corresponding author's website (http://lmb.informatik.uni‐freiburg.de/people/ronneber), licensed under the GNU General Public License (GPL) v2. Binaries are provided for Linux and Microsoft Windows. The toolset is written in templated C++, such that it can operate on datasets with any bit‐depth. Due to the consequent use of 64bit addressing, stacks of arbitrary size (i.e. larger than 4 GB) can be stitched. The runtime on a standard desktop computer is in the range of a few minutes. A user friendly interface for advanced manual interaction and visualization is also available.
Dental enamel birefringence for a wide mineral content range and for different immersion media's refractive indexes: an improved mathematical interpretation
Authors: SOUSA F.B. , VIANNA S.S. , SANTOS‐MAGALHÃES N.S.
Published: January 2009

The aim of this study is to extend, for a larger range of mineral volume (V1) and different aqueous immersion media, the model for calculating the refractive index of the non‐mineral phase of the human dental enamel proposed by Sousa et al. Published experimental birefringence data of carious and developing human enamel in air and aqueous immersion media with different refractive indexes were interpreted. For 48%≤V1≤ 95%, quantitative estimates on the non‐mineral contents consistent with the values described in the literature were derived. New polynomial relationships of the non‐mineral contents as a function of the mineral content (48%≤V1≤ 95%) are introduced, which allows computing the theoretical mean enamel birefringence in water and air for most of the points of developing, carious and mature enamel with a difference of one order of magnitude in relation to the classical model for the non‐mineral content's refractive index and closer to the experimental data. For enamel birefringence in immersion media other than water and air, a less expressive improvement was obtained. Perspectives for future studies are discussed.
Simple 3D images from fossil and Recent micromaterial using light microscopy
Authors: HAUG J.T. , HAUG C. , MAAS A. , FAYERS S.R. , TREWIN N.H. , WALOSZEK D.
Published: January 2009

We present a technique for extracting 3D information from small‐scale fossil and Recent material and give a summary of other contemporary techniques for 3D methods of investigation. The only hardware needed for the here‐presented technique is a microscope that can perform dark field and/or differential interference contrast with a mounted digital camera and a computer. Serial images are taken while the focus is successively shifted from the uppermost end of the specimen to the lowermost end, resulting in about 200 photographs. The data are then processed almost completely automatically by successive use of three freely available programs. Firstly, the stack of images is aligned by the use of CombineZM, which is used to produce a combined image with a high depth of field. Secondly, the aligned images are cropped and sharp edges extracted with the aid of ImageJ. Thirdly, although ImageJ is also capable of producing 3D representations, we preferred to process the image stack further using osirix as it has the facility to export various formats. One of the interesting export formats is a virtual Quicktime movie file (QTVR), which can be used for documentation, and stereo images can also be produced from this Quicktime VR. This method is easy to apply and can be used for documenting specimens in 3D (at least some aspects) without having to prepare them. Therefore, it is particularly useful as a safe method for documenting limited material, before using methods that may destroy the specimen of interest, or to investigate type material that cannot be treated with any preparatory technique. As light microscopes are available in most labs and free computer programs are easily accessible, this method can be readily applied.
Interface study by dual‐beam FIB‐TEM in a pressureless infiltrated Al(Mg)–Al2O3 interpenetrating composite
Authors: CHANG H. , HIGGINSON R.L. , BINNER J.G.P.
Published: January 2009

This paper considers the microstructures of an Al(Mg)–Al2O3 interpenetrating composite produced by a pressureless infiltration technique. It is well known that the governing principle in pressureless infiltration in Al–Al2O3 system is the wettability between the molten metal and the ceramic phase; however, the infiltration mechanism is still not well understood. The objective of this research was to observe the metal–ceramic interface to understand the infiltration mechanism better. The composite was produced using an Al‐8 wt% Mg alloy and 15% dense alumina foams at 915°C in a flowing N2 atmosphere. After infiltration, the composite was characterized by a series of techniques. Thin‐film samples, specifically produced across the Al(Mg)–Al2O3 interface, were prepared using a dual‐beam focussed ion beam and subsequently observed using transmission electron microscopy. XRD scan analysis shows that Mg3N2 formed in the foam at the molten alloy–ceramic infiltration front, whereas transmission electron microscopy analysis revealed that fine AlN grains formed at the metal–ceramic interface and MgAl2O4 and MgSi2 grains formed at specific points. It is concluded that it is the reactions between Al, Mg and the N2 atmosphere that improve the wettability between molten Al and Al2O3 and induce spontaneous infiltration.