bluuebunny/crossref_metadata_2025 huggingface dataset:
Ocular late effects in childhood and adolescent cancer survivors: A report from the childhood cancer survivor study
Authors: Whelan Kimberly F. , Stratton Kayla , Kawashima Toana , Waterbor John W. , Castleberry Robert P. , Stovall Marilyn , Sklar Charles A. , Packer Roger J. , Mitby Pauline , Aitken Candice L. , Blatt Julie , Robison Leslie L. , Mertens Ann C.
Published: September 2009

Introduction

Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.

Procedure

The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of six ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings.

Results

Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR: 10.8; 95% CI: 6.2–18.9), glaucoma (RR: 2.5; 95% CI: 1.1–5.7), legal blindness (RR: 2.6; 95% CI: 1.7–4.0), double vision (RR: 4.1; 95% CI: 2.7–6.1), and dry eyes (RR: 1.9; 95% CI: 1.6–2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose‐dependent manner. Risk of cataracts were also associated with radiation 3,000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0–14.3), temporal lobe (RR: 9.4; 95% CI: 5.6–15.6), and exposure to prednisone (RR: 2.3; 95% CI: 1.6–3.4).

Conclusions

Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long‐term follow‐up is needed to evaluate potential progression of ocular deficits and impact on quality of life. Pediatr Blood Cancer 2010; 54:103–109. © 2009 Wiley‐Liss, Inc.
Long‐term population‐based divorce rates among adult survivors of childhood cancer in Britain
Authors: Frobisher Clare , Lancashire Emma R. , Winter David L. , Taylor Aliki J. , Reulen Raoul C. , Hawkins Michael M.
Published: September 2009

Background

Previously from the British Childhood Cancer Survivor Study (BCCSS) it was seen that adult survivors of childhood cancer were less likely to marry than the general population. The objectives of this study were to assess the number of childhood cancer survivors from the BCCSS who were currently divorced or separated, examine factors associated with marriage dissolution and compare survivor divorce rates to population rates.

Procedure

The BCCSS is a population‐based cohort of 18,119 individuals diagnosed with cancer aged 0–14 years between 1940 and 1991, and survived at least 5 years. 14,539 were alive, aged 16 years or over and eligible to receive a questionnaire, which ascertained marital status.

Results

From 8,155 survivors, who were aged at least 20 years at questionnaire completion, the proportions currently divorced and divorced or separated were 13.5% and 18.1%, respectively. Only current age, educational attainment and age at marriage were associated with divorce, and for divorce and separation status only age at marriage (P < 0.05). Overall the survivors were no different to the general population for being currently divorced (odds ratio (OR) (95% confidence intervals (95% CI)): 0.94 (0.81–1.10)). However, the survivors overall (OR (95% CI): 0.82 (0.72–0.94)), and separately for those diagnosed with non‐Hodgkin lymphoma (OR (95% CI): 0.55 (0.34–0.89)) and leukaemia (OR (95% CI): 0.70 (0.52–0.95)), were less likely to be currently divorced or separated than the general population.

Conclusions

It is reassuring that survivors do not experience more divorce than the general population, and that no cancer or treatment factors were shown to be associated with marriage dissolution. Pediatr Blood Cancer 2010; 54:116–122. © 2009 Wiley‐Liss, Inc.
Quantifying the evolutionary divergence of protein structures: The role of function change and function conservation
Authors: Pascual‐García Alberto , Abia David , Méndez Raúl , Nido Gonzalo S. , Bastolla Ugo
Published: September 2009

The molecular clock hypothesis, stating that protein sequences diverge in evolution by accumulating amino acid substitutions at an almost constant rate, played a major role in the development of molecular evolution and boosted quantitative theories of evolutionary change. These studies were extended to protein structures by the seminal paper by Chothia and Lesk, which established the approximate proportionality between structure and sequence divergence. Here we analyse how function influences the relationship between sequence and structure divergence, studying four large superfamilies of evolutionarily related proteins: globins, aldolases, P‐loop and NADP‐binding. We introduce the contact divergence, which is more consistent with sequence divergence than previously used structure divergence measures. Our main findings are: (1) Small structure and sequence divergences are proportional, consistent with the molecular clock. Approximate validity of the clock is also supported by the analysis of the clustering coefficient of structure similarity networks. (2) Functional constraints strongly limit the structure divergence of proteins performing the same function and may allow to identify incomplete or wrong functional annotations. (3) The rate of structure versus sequence divergence is larger for proteins performing different functions than for proteins performing the same function. We conjecture that this acceleration is due to positive selection for new functions. Accelerations in structure divergence are also suggested by the analysis of the clustering coefficient. (4) For low sequence identity, structural diversity explodes. We conjecture that this explosion is related to functional diversification. (5) Large indels are almost always associated with function changes. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Auditing global logistics operations—A process safety focus
Authors: Green Michael R. , Lide Rick
Published: September 2009

This article discusses an approach for auditing logistics operations using the principles encompassed within BP's Safety and Operations (S&O) Audit Program and will feature an emphasis on process safety. The article concludes with a hypothetical case study to help illustrate portions of the process.

This is a general audit process overview that includes sampling strategy, sampling and testing plan, daily audit schedule, field audit, and verification. This detailed description will help anyone to utilize this logistics audit process effectively. © 2009 American Institute of Chemical Engineers Process Saf Prog, 2010
Effectiveness of a 5‐Day External Stenting Protocol on Urological Complications After Renal Transplantation
Authors: Minnee Robert C. , Bemelman Frederike J. , Laguna Pes Pilar P. , ten Berge Ineke J. M. , Legemate Dink A. , Idu Mirza M.
Published: September 2009

Background

Ureteral stents are successful in reducing urological complications after renal transplantation. However, the optimal duration and method of stenting have not yet been clarified. The objective of the present study was to investigate the frequency of urological complications when a 5‐day external stented ureterocystostomy protocol was followed.

Methods

A single‐center nonrandomized analysis of 392 kidney transplantations between June 2003 and June 2007 was conducted. From July 2005 all 196 renal transplant recipients received a 5‐day external stented ureterocystostomy. A urological complication was defined as any cause leading to the placement of a percutaneous nephrostomy catheter and/or surgical revision of the ureterocystostomy.

Results

In the non‐stented group, 21 of the 196 patients (10.7%) developed a urological complication compared to 13 patients (6.6%) in the stented group (p = 0.151). In the stented group, 2 of the 66 recipients of a living donor transplant (3.0%) developed a urological complication compared to 8 of the 59 recipients (13.6%) in the non‐stented group (P = 0.030). Eleven of 130 recipients of a deceased donor transplant (8.5%) in the stented group developed a urological complication, compared to 13 of the 137 recipients (9.5%) in the non‐stented group (P = 0.769). The surgical revision rate of the stented and the non‐stented group was 5/13 39% and 6/21 29%, respectively.

Conclusions

A 5‐day routine external stent protocol is efficacious in living donor renal transplantation in preventing early postoperative ureter obstruction, but this stenting period seems inadequate for deceased donor renal transplantation.
Detection of Pulmonary Embolism in the Postoperative Orthopedic Patient Using Spiral CT Scans
Authors: Kim Han Jo , Walcott-Sapp Sarah , Leggett Kristi , Bass Anne , Adler Ronald S. , Pavlov Helene , Westrich Geoffrey H.
Published: September 2009

Orthopedic surgery is associated with a significant risk of postoperative pulmonary embolism (PE) and/or deep vein thrombosis (DVT). This study was performed to compare the clinical presentations of a suspected versus a documented PE/DVT and to determine the actual incidence of PE/DVT in the post-operative orthopedic patient in whom CT was ordered. All 695 patients at our institution who had a postoperative spiral CT to rule out PE/DVT from March 2004 to February 2006 were evaluated and information regarding their surgical procedure, risk factors, presenting symptoms, location of PE/DVT, and anticoagulation were assessed. Statistical analysis was performed using an independent samples t test with a two-tailed p value to examine significant associations between the patient variables and CT scans positive for PE. Logistic regression models were used to determine which variables appeared to be significant predictors of a positive chest CT. Of 32,854 patients admitted for same day surgery across all services, 695 (2.1%) had a postoperative spiral CT based on specific clinical guidelines. The incidence of a positive scan was 27.8% (193/695). Of these, 155 (22.3%) scans were positive for PE only, 24 (3.5%) for PE and DVT, and 14 (2.0%) for DVT only. The most common presenting symptoms were tachycardia (56%, 393/695), low oxygen saturation (48%, 336/695), and shortness of breath (19.6%, 136/695). Symptoms significantly associated with DVT were syncope and chest pain. A past medical history of PE/DVT was the only significant predictor of a positive scan. Patients who have a history of thromboembolic disease should be carefully monitored in the postoperative setting.
Effect of rapeseed oil-derived plant sterol and stanol esters on atherosclerosis parameters in cholesterol-challenged heterozygous Watanabe Heritable Hyperlipidaemic rabbits
Authors: Schrøder Malene , Fricke Christiane , Pilegaard Kirsten , Poulsen Morten , Wester Ingmar , Lütjohann Dieter , Mortensen Alicja
Published: September 2009

Rapeseed oil (RSO) is a novel source of plant sterols, containing the unique brassicasterol in concentrations higher than allowed for plant sterol blends in food products in the European Union. Effects of RSO sterols and stanols on aortic atherosclerosis were studied in cholesterol-fed heterozygous Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma campestanol (P < 0·001) and sitostanol (P < 0·001) and aortic campestanol (P < 0·05) compared with controls. Feeding RSO sterol esters increased concentrations of plasma campesterol (P < 0·001), sitosterol (P < 0·001) and brassicasterol (P < 0·001) and aortic campesterol (P < 0·01). Significantly lower plasma cholesterol (P < 0·001) was recorded in the treated groups after 3 weeks and throughout the study. LDL-cholesterol was reduced 50 % in the high-dose RSO sterol ester (P < 0·01) and high-dose RSO stanol ester (P < 0·001) groups compared with controls. Atherosclerotic lesions were found in three rabbits in each of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P < 0·001) in response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration of brassicasterol were well tolerated. They were hypocholesterolaemic and inhibited experimental atherosclerosis in cholesterol-fed Hh-WHHL rabbits. A significant uptake of plant sterols into the blood and incorporation of campesterol and campestanol into aortic tissue was recorded.
Maternal folic acid supplement use in early pregnancy and child behavioural problems: The Generation R Study
Authors: Roza Sabine J. , van Batenburg-Eddes Tamara , Steegers Eric A. P. , Jaddoe Vincent W. V. , Mackenbach Johan P. , Hofman Albert , Verhulst Frank C. , Tiemeier Henning
Published: September 2009

Folate deficiency during embryogenesis is an established risk factor for neural tube defects in the fetus. An adequate folate nutritional status is also important for normal fetal growth and brain development. The aim of the present research was to study the association between folic acid use of the mother during pregnancy and child behavioural development. Within a population-based cohort, we prospectively assessed folic acid supplement use during the first trimester by questionnaire. Child behavioural and emotional problems were assessed with the Child Behaviour Checklist at the age of 18 months in 4214 toddlers. Results showed that children of mothers who did not use folic acid supplements in the first trimester had a higher risk of total problems (OR 1·44; 95 % CI 1·12, 1·86). Folic acid supplement use protected both from internalising (OR of no supplement use 1·65; 95 % CI 1·24, 2·19) and externalising problems (OR 1·45; 95 % CI 1·17, 1·80), even when adjusted for maternal characteristics. Birth weight and size of the fetal head did not mediate the association between folic acid use and child behaviour. In conclusion, inadequate use of folic acid supplements during early pregnancy may be associated with a higher risk of behavioural problems in the offspring. Folic acid supplementation in early pregnancy, aimed to prevent neural tube defects, may also reduce mental health problems in children.
The impact of tap connection on water use: the case of household water consumption in Dakar, Senegal
Authors: BRIAND ANNE , NAUGES CÉLINE , STRAND JON , TRAVERS MURIEL
Published: September 2009

Predicting residential water demand for non-connected households that obtain connections is a crucial issue for water planners in developing countries. We propose a technique derived from Heckman (1976) to accurately measure the expected increase in water use due to access to tap water while controlling for differences in characteristics between connected and non-connected households. Illustration is made on a cross section of 246 households from Dakar, Senegal. We show that getting a tap connection induces an expected increase in water use of 26 L per capita per day.
Television viewing, computer game play and book reading during meals are predictors of meal skipping in a cross-sectional sample of 12-, 14- and 16-year-olds
Authors: Custers Kathleen , Van den Bulck Jan
Published: September 2009

Objective

To examine whether television viewing, computer game playing or book reading during meals predicts meal skipping with the aim of watching television, playing computer games or reading books (media meal skipping).

Design

A cross-sectional study was conducted using a standardized self-administered questionnaire. Analyses were controlled for age, gender and BMI.

Setting

Data were obtained from a random sample of adolescents in Flanders, Belgium.

Subjects

Seven hundred and ten participants aged 12, 14 and 16 years.

Results

Of the participants, 11·8 % skipped meals to watch television, 10·5 % skipped meals to play computer games and 8·2 % skipped meals to read books. Compared with those who did not use these media during meals, the risk of skipping meals in order to watch television was significantly higher for those children who watched television during meals (2·9 times higher in those who watched television during at least one meal a day). The risk of skipping meals for computer game playing was 9·5 times higher in those who played computer games weekly or more while eating, and the risk of meal skipping in order to read books was 22·9 times higher in those who read books during meals less than weekly. The more meals the respondents ate with the entire family, the less likely they were to skip meals to watch television.

Conclusions

The use of media during meals predicts meal skipping for using that same medium. Family meals appear to be inversely related to meal skipping for television viewing.
Intensified upwelling over a widened shelf in the northeastern South China Sea
Authors: Gan Jianping , Cheung Anson , Guo Xiaogang , Li Li
Published: September 2009

Observational and three‐dimensional modeling studies reveal that the intensified upwelling in the northeastern South China Sea (NSCS) is formed as a result of intensified upslope advection of dense deep waters that cross the middle shelf toward the inner shelf over a distinctly eastward widened shelf. The strongest advection occurs over the converging isobaths near the head of the widened shelf. As these dense deep waters advance shoreward, they are advected downstream by the quickly developed upwelling current over the inner shelf and eventually outcropped at the lee of a coastal cape. Dynamically, the shoreward cross‐isobath transport over the widened shelf is geostrophically enhanced by a quasi‐barotropic negative (westward) along‐isobath pressure gradient force as a result of the net rate of the momentum influx and by an intensified bottom frictional transport owing to the flow confluence near the head of the widened shelf. A negative pressure gradient also exists at the lee of the coastal cape over the inner shelf and locally amplifies shoreward motion. Induced by the respective widened shelf and the coastal promontory, the along‐isobath variations of cross‐isobath transport in the water column over the middle and inner shelves interactively characterize intensified upwelling in the NSCS.
THEMIS observations of the near‐Earth plasma sheet during a substorm
Authors: Tang C. L. , Li Z. Y. , Angelopoulos V. , Mende S. B. , Glassmeier K. H. , Donovan E. , Russell C. T. , Lu L.
Published: September 2009

We present observations of a substorm on 13 March 2008 by Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft in the near‐Earth tail during the plasma sheet expansion evidenced by increase in the plasma density and temperature. The main features of the event are as follows: (1) Cross‐tail current reduction or current disruption (CD) was observed in the near‐Earth tail at X ∼ −8.0 RE and Y ∼ 2.0 RE, marked by a sharp drop of ∣Bx∣ and accompanied by sharp increases in the plasma density and temperature, manifesting a rapid expansion (recovery) of the local plasma sheet. During the course of the plasma sheet expansion, the propagation speed of the dipolarization is ∼48 km/s in tailward direction and ∼35 km/s in azimuthal direction. (2) In the inner edge of the plasma sheet, slow flux pileup is observed. The magnetic flux pileup is characterized by continuous enhancement of Bz and Bt and a reduction of the plasma density, pressure Pth, and β in the flow‐braking region. The tailward moving plasma sheet expansion (CD) is also passing across the flow‐braking region. In short, the dipolarization in the inner edge of the plasma sheet can be attributed to CD, while the tailward progression of dipolarization in the flow‐braking region can be attributed to magnetic flux pileup. (3) A sharp decrease in the magnitude of Bx at P1 (−13.1 RE, 2.5 RE, −0.56 RE) prior to the dipolarization at P5 is difficult to explain as part of the outward evolution of the CD. The rapid change in the magnetic field topology, and signatures of earthward flows and dipolarization observed at P1 prior to Pi2 onset may be caused by inward motion of flux from magnetic reconnection in the midtail (20–30 RE). Tail reconnection prior to substorm expansion can result in a sudden change of the near‐Earth configuration, which may result in instabilities related to the onset of CD.
Spatiotemporal variability of satellite‐derived primary production in the South China Sea, 1998–2006
Authors: Tan Sai‐Chun , Shi Guang‐Yu
Published: September 2009

This study examined the spatiotemporal variability of ocean primary production (OPP) in the South China Sea (SCS) for the period 1998–2006; OPP was estimated using a satellite primary production model. Estimated OPP showed variability both in multiyear averages and interannually. Peaks in average OPP in the SCS appeared in winter (January) and summer (August), with the winter peak greater than the summer peak. As for the whole SCS, both along the coast at Guangdong Province and in the central basin region, the maximum OPP peak occurred in winter with a secondary peak observed during summer. OPP values were approximately three times higher near the coastal regions than in the central basin regions. High OPP in the western SCS occurred in every summer season (June–August) and was related to the surface circulation, upwelling, and seasonal rain. A jet of high OPP that developed offshore in the western SCS was associated with coastal upwelling driven by the southwest monsoon, Vietnamese offshore current, and discharges from the Mekong River. Monthly averaged OPP from January 1998 to December 2006 in the western SCS had lowest values during the summer of 1998. This anomalous event coincided with the 1997–1998 El Niño event. Spatial and temporal variability of OPP in the SCS is influenced by physicochemical environmental conditions, such as nutrients, the depth of the mixed layer, the seasonally reversed monsoon, river discharge, upwelling, and coastal currents.
Estimating lightning current moment waveforms from satellite optical measurements
Authors: Adachi Toru , Cummer Steven A. , Li Jingbo , Takahashi Yukihiro , Hsu Rue‐Ron , Su Han‐Tzong , Chen Alfred B. , Mende Stephen B. , Frey Harald U.
Published: September 2009

From July 2004 to June 2007, the FORMOSAT‐2/ISUAL spectrophotometer and Duke magnetometer observed clear optical and radio signatures of 12 sprite‐producing lightning events. In 10 of these, 777.4‐nm luminosity normalized to a distance of 3000 km was almost linearly correlated with current moment with a scaling factor of ∼0.82 MR/kAkm. This finding provides a possible new way to remotely measure lightning current moment, which is critical for understanding the production of sprites, through satellite‐based optical measurements. The remaining 2 events had anomalously large scaling factors of ∼3 and ∼8 MR/kAkm. The concurrent images showed two coincident bright cores of lightning, which suggests complex in‐cloud lightning processes may sometimes affect the optical‐radio relationship.
Radiative transfer in CO2‐rich paleoatmospheres
Authors: Halevy I. , Pierrehumbert R. T. , Schrag D. P.
Published: September 2009

Calculations of radiative transfer in CO2‐rich atmospheres are central to modeling the early climate of Earth and Mars. Line‐by‐line radiative transfer models are the most accurate means of carrying out such calculations and provide the basis for all other radiative transfer approaches. We examine the sensitivity of line‐by‐line results to three parameterizations of line and continuum absorption by CO2, all of which yield essentially identical radiation fluxes at low CO2 abundance. However, when applied to atmospheres containing 0.1–5 bars of CO2, appropriate for early Earth and Mars, the outgoing longwave radiation calculated with the three parameterizations differs by as much as 40 W m−2. In addition, the choice of parameters for CO2 absorption affects the sensitivity of the calculations to infrared absorption by trace gases other than CO2. Our findings imply that previous estimates of the amount of CO2 required to maintain relatively warm temperatures throughout Earth's early history and during episodes in the early history of Mars are highly uncertain. Despite these uncertainties, we conclude that early Mars probably required other infrared absorbers to reach super‐freezing surface temperatures, while for the early Earth, this is not necessarily the case.
Ozone depletion, water vapor increase, and PSC generation at midlatitudes by the 2008 major stratospheric warming
Authors: Flury T. , Hocke K. , Haefele A. , Kämpfer N. , Lehmann R.
Published: September 2009

The ground‐based microwave radiometers GROMOS and MIAWARA at Bern (Switzerland) continuously measure ozone and water vapor profiles from 20 to 70 km altitude. A major sudden stratospheric warming occurred around 19 February 2008 with minimal temperatures of 189 K at 40 hPa and maximal temperatures of 300 K at 4 hPa. During the stratospheric warming the Swiss ground‐based radiometers observed a depletion of ozone and an enhancement of water vapor while NASA's CALIPSO satellite instrument measured a large PSC area over Europe. Ozone depletion in the lower stratosphere is explained by transport of ozone poor air from the cold polar vortex. The depletion of upper stratospheric ozone is caused by a sudden temperature increase of about 50 K. A simulation of a chemical box model confirms that a major fraction of the observed decrease of the ozone mixing ratio at 4 hPa can be explained by the effect of the increasing temperature on the ozone chemistry. The chemical ozone destruction is dominated by a catalytic NOx cycle, which is more efficient at higher temperatures. The water vapor enhancement can be explained by transport processes. The rather unusual occurrence of a PSC and a sudden stratospheric warming at midlatitudes suggest that further monitoring of the Earth's middle atmosphere is required for the timely detection of unexpected problems due to ozone loss and climate change.
Changes in land use alter the structure of bacterial communities in Western Amazon soils
Authors: da C Jesus Ederson , Marsh Terence L , Tiedje James M , de S Moreira Fatima M
Published: September 2009

Correction to: The ISME Journal (2009) 3, 1004–1011; doi:10.1038/ismej.2009.47 Since the publication of this paper, the authors have noticed an error in the accession numbers on page 2. The correct text is shown here. The authors would like to apologise for this error. Libraries were built for samples from primary forest (GenBank accession no.
Secretory phospholipase A2 promotes MMP‐9‐mediated cell death by degrading type I collagen via the ERK pathway at an early stage of chondrogenesis
Authors: Choi Young‐Ae , Kim Dong‐Kyun , Bang Ok‐Sun , Kang Shin‐Sung , Jin Eun‐Jung
Published: September 2009

Background information. sPLA2 (secretory phospholipase A2) has been implicated in a wide range of cellular responses, including cell proliferation and ECM (extracellular matrix) remodelling. Even though ECM remodelling is an essential step for chondrogenesis, the expression and functions of sPLA2 during chondrogenesis have not been studied.

Results. In the present study, for the first time, we detect the secretion of sPLA2 during limb development and suggest that sPLA2 influences the proliferation and/or survival of limb mesenchymal cells. Treatment of wing bud mesenchymal cells with exogenous sPLA2 promoted cell death by activating MMP‐9 (matrix metalloproteinase‐9) and increasing type I collagen degradation. The additive chondro‐inhibitory actions were induced by co‐treatment of mp‐BSA (p‐aminophenyl‐mannopyranoside‐BSA), a known ligand of the mannose receptor. Chondro‐inhibitory actions by sPLA2 were prevented by functional blocking of FcRY (chicken yolk sac IgY receptor), a mannose receptor family member that is the orthologue of the mammalian PLA2 (phospholipase A2) receptor and by inhibition of ERK (extracellular‐signal‐regulated kinase) activity.

Conclusions. Taken together, our results suggest that elevated levels of sPLA2 secreted by wing bud mesenchymal cells promote type I collagen degradation by MMP‐9 in a manner typical of receptor‐mediated signalling and that these events lead to cell death.
Leishmania donovani Ran-GTPase interacts at the nuclear rim with linker histone H1
Authors: Smirlis Despina , Boleti Haralabia , Gaitanou Maria , Soto Manuel , Soteriadou Ketty
Published: September 2009

Ran-GTPase regulates multiple cellular processes such as nucleocytoplasmic transport, mitotic spindle assembly, nuclear envelope assembly, cell-cycle progression and the mitotic checkpoint. The leishmanial Ran protein, in contrast with its mammalian counterpart which is predominately nucleoplasmic, is localized at the nuclear rim. The aim of the present study was to characterize the LdRan (Leishmania donovani Ran) orthologue with an emphasis on the Ran–histone association. LdRan was found to be developmentally regulated, expressed 3-fold less in the amastigote stage. LdRan overexpression caused a growth defect linked to a delayed S-phase progression in promastigotes as for its mammalian counterpart. We report for the first time that Ran interacts with a linker histone, histone H1, in vitro and that the two proteins co-localize at the parasite nuclear rim. Interaction of Ran with core histones H3 and H4, creating in metazoans a chromosomal Ran-GTP gradient important for mitotic spindle assembly, is speculative in Leishmania spp., not only because this parasite undergoes a closed mitosis, but also because the main localization of LdRan is different from that of core histone H3. Interaction of Ran with the leishmanial linker histone H1 (LeishH1) suggests that this association maybe involved in modulation of pathways other than those documented for the metazoan Ran–core histone association.
Structural insight on the control of urea synthesis: identification of the binding site forN-acetyl-L-glutamate, the essential allosteric activator of mitochondrial carbamoyl phosphate synthetase
Authors: Pekkala Satu , Martínez Ana I. , Barcelona Belén , Gallego José , Bendala Elena , Yefimenko Igor , Rubio Vicente , Cervera Javier
Published: September 2009

NAG (N-acetyl-L-glutamate), the essential allosteric activator of the first urea cycle enzyme, CPSI (carbamoyl phosphate synthetase I), is a key regulator of this crucial cycle for ammonia detoxification in animals (including humans). Automated cavity searching and flexible docking have allowed identification of the NAG site in the crystal structure of human CPSI C-terminal domain. The site, a pocket lined by invariant residues and located between the central β-sheet and two α-helices, opens at the β-sheet C-edge and is roofed by a three-residue lid. It can tightly accommodate one extended NAG molecule having the δ-COO− at the pocket entry, the α-COO− and acetamido groups tightly hydrogen bonded to the pocket, and the terminal methyl of the acetamido substituent surrounded by hydrophobic residues. This binding mode is supported by the observation of reduced NAG affinity upon mutation of NAG-interacting residues of CPSI (recombinantly expressed using baculovirus/insect cells); by the fine-mapping of the N-chloroacetyl-L-glutamate photoaffinity labelling site of CPSI; and by previously established structure–activity relationships for NAG analogues. The location of the NAG site is identical to that of the weak bacterial CPS activator IMP (inosine monophosphate) in Escherichia coli CPS, indicating a common origin for these sites and excluding any relatedness to the binding site of the other bacterial CPS activator, ornithine. Our findings open the way to the identification of CPSI deficiency patients carrying NAG site mutations, and to the possibility of tailoring the activator to fit a given NAG site mutation, as exemplified here with N-acetyl-L(±)-β-phenylglutamate for the W1410K CPSI mutation.
Mutational analysis of human heat-shock transcription factor 1 reveals a regulatory role for oligomerization in DNA-binding specificity
Authors: Takemori Yukiko , Enoki Yasuaki , Yamamoto Noritaka , Fukai Yo , Adachi Kaori , Sakurai Hiroshi
Published: September 2009

HSF (heat-shock transcription factor) trimers bind to the HSE (heat-shock element) regulatory sequence of target genes and regulate gene expression. A typical HSE consists of at least three contiguous inverted repeats of the 5-bp sequence nGAAn. Yeast HSF is able to recognize discontinuous HSEs that contain gaps in the array of the nGAAn sequence; however, hHSF1 (human HSF1) fails to recognize such sites in vitro, in yeast and in HeLa cells. In the present study, we isolated suppressors of the temperature-sensitive growth defect of hHSF1-expressing yeast cells. Intragenic suppressors contained amino acid substitutions in the DNA-binding domain of hHSF1 that enabled hHSF1 to regulate the transcription of genes containing discontinuous HSEs. The substitutions facilitated hHSF1 oligomerization, suggesting that the DNA-binding domain is important for this conformational change. Furthermore, other oligomerization-prone derivatives of hHSF1 were capable of recognizing discontinuous HSEs. These results suggest that modulation of oligomerization is important for the HSE specificity of hHSF1 and imply that hHSF1 possesses the ability to bind to and regulate gene expression via various types of HSEs in diverse cellular processes.
miRNPs: versatile regulators of gene expression in vertebrate cells
Authors: Steitz Joan A. , Vasudevan Shobha
Published: September 2009

TNFα (tumour necrosis factor α) mRNA bears in its 3′-UTR (untranslated region) a conserved ARE (AU-rich element), a signal that exerts tight post-transcriptional control over the expression of TNFα and other cytokines. We found that the TNFα ARE increases translational efficiency when cell growth is arrested, a physiologically relevant state occurring during inflammation, angiogenesis and monocyte differentiation. Under these conditions, called quiescence, the miRNP (microribonucleoprotein)-associated proteins FXR1 (Fragile X mental retardation-related protein 1) and AGO2 (Argonaute 2), which are usually considered negative regulators, are transformed into effector molecules that bind the ARE to activate translation. We then identified a specific miRNA (microRNA) that directs the association of AGO2 and FXR1 with the ARE during translational up-regulation. Two other well-characterized miRNAs likewise promote translation activation in quiescent or in contact-inhibited cells; yet, they repress translation in proliferating cells in the late S/G2-phase. We conclude that translational regulation by miRNPs oscillates between repression and activation as a function of the cell cycle. The activating role of miRNAs is now being confirmed in the immature Xenopus oocyte, which mimics the quiescent state.
The emerging complexity of protein ubiquitination
Authors: Komander David
Published: September 2009

Protein ubiquitination and protein phosphorylation are two fundamental regulatory post-translational modifications controlling intracellular signalling events. However, the ubiquitin system is vastly more complex compared with phosphorylation. This is due to the ability of ubiquitin to form polymers, i.e. ubiquitin chains, of at least eight different linkages. The linkage type of the ubiquitin chain determines whether a modified protein is degraded by the proteasome or serves to attract proteins to initiate signalling cascades or be internalized. The present review focuses on the emerging complexity of the ubiquitin system. I review what is known about individual chain types, and highlight recent advances that explain how the ubiquitin system achieves its intrinsic specificity. There is much to be learnt from the better-studied phosphorylation system, and many key regulatory mechanisms underlying control by protein phosphorylation may be similarly employed within the ubiquitin system. For example, ubiquitination may have important allosteric roles in protein regulation that are currently not appreciated.
Structural aspects of Rab6–effector complexes
Authors: Fernandes Humberto , Franklin Edward , Recacha Rosario , Houdusse Anne , Goud Bruno , Khan Amir R.
Published: September 2009

The small GTPase Rab6 regulates vesicle trafficking at the level of Golgi. Recently, the crystal structures of Rab6 in complexes with two unrelated effectors have been determined. The structure of Rab6a-GTP in complex with a 378-residue internal fragment of the effector Rab6IP1 (Rab6-interacting protein 1) has been solved. In addition, the structure of Rab6 with the golgin, GCC185, has also been determined. In both complexes, two α-helices from the effector mediate binding to switch I, switch II and the interswitch region of Rab6. Comparisons of the complexes reveal significant conformational changes in the conserved hydrophobic triad of Rab6. Thus conformational flexibility in the triad mediates recognition of compositionally distinct α-helical coiled coils, providing a rationale for the promiscuity of Rab6 in effector recruitment.
GRAF1-dependent endocytosis
Authors: Doherty Gary J. , Lundmark Richard
Published: September 2009

The role of endocytosis in controlling a multitude of cell biological events is well established. Molecular and mechanistic characterization of endocytosis has predominantly focused on CME (clathrin-mediated endocytosis), although many other endocytic pathways have been described. It was recently shown that the BAR (Bin/amphiphysin/Rvs) and Rho GAP (GTPase-activating protein) domain-containing protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) is found on prevalent, pleiomorphic endocytic membranes, and is essential for the major, clathrin-independent endocytic pathway that these membranes mediate. This pathway is characterized by its ability to internalize GPI (glycosylphosphatidylinositol)-anchored proteins, bacterial toxins and large amounts of extracellular fluid. These membrane carriers are highly dynamic and associated with the activity of the small G-protein Cdc42 (cell division cycle 42). In the present paper, we review the role of GRAF1 in this CLIC (clathrin-independent carrier)/GEEC (GPI-anchored protein-enriched early endocytic compartment) endocytic pathway and discuss the current understanding regarding how this multidomain protein functions at the interface between membrane sculpting, small G-protein signalling and endocytosis.
Lactate damages primary hippocampal neurons in vitro
Authors: Sepehr Arian , Mohseni Simin
Published: September 2009

In the present study, rat primary cultures were used to study the effect of lactate on the survival of hippocampal neurons in the presence or absence of glucose. Our results showed no extensive cell damage under glucose‐free conditions compared with glucose‐rich conditions. Addition of 10 and 50 mM lactate to glucose‐free and glucose‐rich media increased the cell damage significantly, as observed by morphology and lactate dehydrogenase activity. The results of the present study suggest that primary neurons in vitro are not sensitive to glucose deficiency and the presence of lactate damages the neurons in a concentration‐dependent manner.
Using Institutional Theory with Sensemaking Theory: A Case Study of Information System Implementation in Healthcare
Authors: Jensen Tina Blegind , Kjærgaard Annemette , Svejvig Per
Published: September 2009

Institutional theory has proven to be a central analytical perspective for investigating the role of social and historical structures of information systems (IS) implementation. However, it does not explicitly account for how organisational actors make sense of and enact technologies in their local context. We address this limitation by exploring the potential of using institutional theory with sensemaking theory to study IS implementation in organisations. We argue that each theoretical perspective has its own explanatory power and that a combination of the two facilitates a much richer interpretation of IS implementation by linking macro- and micro-levels of analysis. To illustrate this, we report from an empirical study of the implementation of an Electronic Patient Record (EPR) system in a clinical setting. Using key constructs from the two theories, our findings address the phenomenon of implementing EPRs at three levels: the organisational field, the organisational/group, and the individual/socio-cognitive level. The study shows how a rationalised myth of an efficient EPR system has travelled from the organisational field to the hospital ward and on to individual doctors. The findings also provide evidence of a strong human agency by showing how doctors enact their work practices and shape the use of the EPR system. The study contributes to IS research by showing the need to address macro-level structures, as well as individual interpretations and practical use situations, in order to identify how and why information systems are adopted by users.
Targeting and clustering of IP3 receptors: Key determinants of spatially organized Ca2+ signals
Authors: Taylor Colin W. , Taufiq-Ur-Rahman  , Pantazaka Evangelia
Published: September 2009

Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca2+ channels that are almost ubiquitously expressed in animal cells. The spatiotemporal complexity of the Ca2+ signals evoked by IP3R underlies their versatility in cellular signaling. Here we review the mechanisms that contribute to the subcellular targeting of IP3R and the dynamic interplay between IP3R that underpin their ability to generate complex intracellular Ca2+ signals.
An investigation of models of the IP3R channel in Xenopus oocyte
Authors: Shuai J. W. , Yang D. P. , Pearson J. E. , Rüdiger S.
Published: September 2009

We consider different models of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) channels in order to fit nuclear membrane patch clamp data of the stationary open probability, mean open time, and mean close time of channels in the Xenopus oocyte. Our results indicate that rather than to treat the tetrameric IP3R as four independent and identical subunits, one should assume sequential binding-unbinding processes of Ca2+ ions and IP3 messengers. Our simulations also favor the assumption that a channel opens through a conformational transition from a close state to an active state.
Prevalence of stochasticity in experimentally observed responses of pancreatic acinar cells to acetylcholine
Authors: Perc Matjaž , Rupnik Marjan , Gosak Marko , Marhl Marko
Published: September 2009

Calcium ions play an important role in both intra- and intercellular signaling. In pancreatic acinar cells intracellular Ca2+ regulates exocytotic secretion and fluid secretion. In this paper we study the typical experimental traces of Ca2+ responses in pancreatic acinar cells obtained in response to the physiological agonist acetylcholine. To determine whether they are stochastic or deterministic in nature, we analyze the traces with methods of nonlinear time series analysis. In particular, by performing surrogate data tests and employing a determinism test for short time series, we show that the responses of pancreatic acinar cells to acetylcholine are stochastic with only faintly expressed deterministic features. Presented results thus corroborate the notion that mathematical models should take stochasticity explicitly into account when describing intra- and intercellular processes, and that indeed further efforts should be directed toward this subject.
Investigating the effects of molecular crowding on Ca2+ diffusion using a particle-based simulation model
Authors: Straube Ronny , Ridgway Douglas
Published: September 2009

Calcium ions (Ca2+) are an important second messenger in eucaryotic cells. They are involved in numerous physiological processes which are triggered by calcium signals in the form of local release events, temporal oscillations, or reaction-diffusion waves. The diffusive spread of calcium signals in the cytosol is strongly affected by calcium-binding proteins (buffers). In addition, the cytosol contains a large number of inert molecules and molecular structures which make it a crowded environment. Here, we investigate the effects of such excluded volumes on calcium diffusion in the presence of different kinds of buffers. We find that the contributions in slowing down Ca2+ diffusion coming from buffering and molecular crowding are not additive, i.e., the reduction in Ca2+ diffusivity due to crowding and buffering together is not the sum of each single contribution. In the presence of Ca2+ gradients and high affinity mobile buffers the effective diffusion coefficient of Ca2+ can be reduced by up to 60% in highly crowded environments. This suggests that molecular crowding may significantly affect the shape of Ca2+ microdomains and wave propagation in cell types with high excluded volume fractions.
Enhanced tunneling spin polarization from ultrathin layers of amorphous CoFe
Authors: Gao Li , Jiang Xin , Rice Philip M. , Parkin Stuart S. P.
Published: September 2009

The tunneling spin polarization of CoFe alloys is directly compared in their amorphous (<∼25–30 Å) and crystalline states using superconducting tunneling spectroscopy measurements of Al95Si5/Al2O3/CoFe junctions. Ultrathin layers of normally crystalline CoFe are made amorphous by sandwiching them between amorphous alumina tunnel barriers and amorphous ferromagnetic CoFeB electrodes. The results show that the tunneling spin polarization is significantly enhanced when the CoFe alloy is made amorphous compared to when it is crystalline. We also show that a postdeposition atomic oxygen treatment of the alumina tunnel barrier significantly enhances the thermal stability of the junctions.
Uniformity and bandgap engineering in hydrogenated nanocrystalline silicon thin films by phosphorus doping for solar cell application
Authors: Li K. H. , Shen W. Z.
Published: September 2009

Micro-Raman mapping with a spatial resolution of micrometer and room-temperature visible photoluminescence (PL) has been carried out on phosphorus-doped hydrogenated nanocrystalline silicon (nc-Si:H) thin films grown by plasma enhanced chemical vapor deposition. Both the thin film uniformity and structural properties, i.e., the distribution of grain sizes and crystalline volume fraction, with different doping concentrations are revealed and physically interpreted based on the growth mechanism. The observed uniformity has been further confirmed by the PL measurements, and the bandgap engineering of the nc-Si:H thin films has been discussed from the dependence of PL peak energy on doping concentration. These results provide implications to realize control of properties of nc-Si:H by P-doping under optimized growth conditions for solar cell application.
Photoassisted high-frequency capacitance-voltage characterization of the Si3N4/GaN interface
Authors: Swenson B. L. , Mishra U. K.
Published: September 2009

A revised method to measure the interface state density of Si3N4/GaN metal-insulator-semiconductor diodes is reported. The wide band gap of GaN suppresses hole generation at room temperature and consequently allows measurements in deep depletion. Using the method outlined in this paper, the total interface state density can be measured throughout the bandgap above the bias in deep depletion utilizing an above bandgap light source. We report a peak interface state density of 5.0×1012 cm−2 eV−1 at ∼0.3 eV using this procedure, whereas the Terman method reports a peak of <2×1011 cm−2 eV−1 for the same Si3N4/GaN metal-insulator-semiconductor diode without illumination.