Gain Insight (gain + insight)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Invasive species of Heracleum in Europe: an insight into genetic relationships and invasion history

DIVERSITY AND DISTRIBUTIONS, Issue 1 2007
árka Jahodová
ABSTRACT Several species of the genus Heracleum (Umbelliferae) were introduced into Europe from south-west Asia in the 19th century and are now widespread in many countries. At least three invasive taxa with unresolved relationships to one another are thought to occur in Europe: Heracleum mantegazzianum Sommier & Levier, H. sosnowskyi Manden, and H. persicum Desf. ex Fischer. They are tall plants forming extensive stands with a high cover. To elucidate genetic relationships between the species, and gain insight into their invasion history, samples were collected from native ranges in Asia and invaded ranges of the three species in Europe and analysed using amplified fragment length polymorphism. Five other Heracleum species were also studied and in total, 189 samples from 72 populations were analysed. The results confirmed that there are three distinct tall Heracleum species invading in Europe. Within each of the three species, plants collected in the invaded range are genetically close to those from their native ranges. A close genetic relationship between the three invasive Heracleum species in Europe was also found. A high overall genetic variability detected in the invaded range suggests that the majority of invading populations were not affected by a genetic bottleneck and that rapid evolution, drift, or hybridization played a role in genetic structuring of invading populations. For H. mantegazzianum, genetic distance of populations in the native range significantly decreased with geographical distance, but not in the invaded range. It is likely that the current pattern of genetic diversity in Europe resulted from multiple introductions of all three species. [source]


Enantiomeric composition of chiral polychlorinated biphenyl atropisomers in dated sediment cores

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2007
Charles S. Wong
Abstract ,Enantiomer fractions (EFs) of seven chiral poly chlorinated biphenyls (PCBs) were measured in dated sediment cores of Lake Hartwell (SC, USA) and Lake Ontario (USA) to detect, quantify, and gain insight regarding microbial reductive dechlorination of PCBs in lake sediments with high and low concentrations, respectively. Lake Hartwell sediments had high total PCBs (5,60 ,g/g), with significantly nonracemic EFs that generally were consistent with those from previous laboratory microcosm reductive dechlorination experiments using sediments from these sites. Thus, stereoselective reductive dechlorination had occurred in situ, including at total PCB concentrations of less than the threshold of approximately 30 to 80 ,g/g suggested as being necessary for reductive dechlorination. Enantiomer fractions of PCBs 91, 95, 132, and 136 in Lake Hartwell cores were significantly correlated both with concentrations of those individual congeners and with total PCB concentration for some sites. This result indicates that enantioselective microbial dechlorination activity increases with higher concentrations within sediments for these congeners. Enantiomer composition reversed with depth for PCBs 91, 132, and 176, suggesting that multiple microbial populations may be present within the same core that are enantioselectively dechlorinating PCBs. Such observations indicate that concentration and time are not the only factors affecting biotransformation, complicating prediction of enantioselectivity. Comparison of EFs with dates suggested biotransformation half-lives of approximately 30 years, which is on the same time scale as sequestration by burial. In contrast, Lake Ontario sediments (maximum total PCBs, 400 ng/g) had racemic or near-racemic amounts of most congeners throughout the core profile, which is consistent with achiral indicators suggesting no microbial biotransformation within Lake Ontario sediments. Thresholds for reductive dechlorination may exist, but they would be at concentrations of less than 30 to 80 ,g/g. [source]


Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients

EUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2006
K. Rejdak
This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NOx) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NOx/Cr ratio and number of NOx peaks was significantly greater in the migraine group compared with controls (P = 0.01 and P = 0.007, respectively). In the second approach, high NOx values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NOx persisted being pulsatile, and migraineurs had more peaks compared with controls (P = 0.01). In seven patients, NOx peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16,7.77; no overlap of 95% CI). In four patients, NOx peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NOx excretion between control and migraine populations, the variable temporal association of NOx peaks and headaches suggests a complex role of NO in this condition. [source]


Kinetic and biochemical analyses on the reaction mechanism of a bacterial ATP-citrate lyase

FEBS JOURNAL, Issue 14 2002
Tadayoshi Kanao
The prokaryotic ATP-citrate lyase is considered to be a key enzyme of the carbon dioxide-fixing reductive tricarboxylic acid (RTCA) cycle. Kinetic examination of the ATP-citrate lyase from the green sulfur bacterium Chlorobium limicola (Cl -ACL), an ,4,4 heteromeric enzyme, revealed that the enzyme displayed typical Michaelis-Menten kinetics toward ATP with an apparent Km value of 0.21 ± 0.04 mm. However, strong negative cooperativity was observed with respect to citrate binding, with a Hill coefficient (nH) of 0.45. Although the dissociation constant of the first citrate molecule was 0.057 ± 0.008 mm, binding of the first citrate molecule to the enzyme drastically decreased the affinity of the enzyme for the second molecule by a factor of 23. ADP was a competitive inhibitor of ATP with a Ki value of 0.037 ± 0.006 mm. Together with previous findings that the enzyme catalyzed the reaction only in the direction of citrate cleavage, these kinetic features indicated that Cl -ACL can regulate both the direction and carbon flux of the RTCA cycle in C. limicola. Furthermore, in order to gain insight on the reaction mechanism, we performed biochemical analyses of Cl -ACL. His273 of the , subunit was indicated to be the phosphorylated residue in the catalytic center, as both catalytic activity and phosphorylation of the enzyme by ATP were abolished in an H273A mutant enzyme. We found that phosphorylation of the subunit was reversible. Nucleotide preference for activity was in good accordance with the preference for phosphorylation of the enzyme. Although residues interacting with nucleotides in the succinyl-CoA synthetase from Escherichia coli were conserved in AclB, AclA alone could be phoshorylated with the same nucleotide specificity observed in the holoenzyme. However, AclB was necessary for enzyme activity and contributed to enhance phosphorylation and stabilization of AclA. [source]


The effect of involvement in participatory research on parent researchers in a Sure Start programme

HEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 6 2006
Ann Rowe M Med Sci BA RN RHVArticle first published online: 24 AUG 200
Abstract Involving service users, patients and members of local communities in health and social care research is becoming increasingly common. However, surprisingly little research has been carried out to examine the experiences of such lay researchers. This paper presents the findings of a study to investigate the experiences of a group of parent researchers involved in a community survey within a UK Sure Start programme. The survey was undertaken to provide insight into the early impact of the programme and inform Sure Start programme expansion. Researchers were recruited from the local community and were given an accredited training programme, before working on the development of the research itself. They took a lead role in the development, data collection, analysis and report writing phases of the survey and have been actively involved with the dissemination of findings. In order to gain insight into the experiences of the lay researchers involved in this work, three separate methods were used to collect data: questionnaires before and after the study, a focus group at the end of the data collection phase and by analysis of personal diaries kept by the parent researchers. Findings reported include lay researchers responses to the accredited training programme, the development of new skills and understanding, access and the conduct of interviews and the impact of the work both for Sure Start and the researchers themselves. Some of the strengths and difficulties of participatory research are discussed and comment made on the extent to which lay involvement impacted on the conduct of the survey. [source]


Empirical orthogonal functions and related techniques in atmospheric science: A review

INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 9 2007
A. Hannachi
Abstract Climate and weather constitute a typical example where high dimensional and complex phenomena meet. The atmospheric system is the result of highly complex interactions between many degrees of freedom or modes. In order to gain insight in understanding the dynamical/physical behaviour involved it is useful to attempt to understand their interactions in terms of a much smaller number of prominent modes of variability. This has led to the development by atmospheric researchers of methods that give a space display and a time display of large space-time atmospheric data. Empirical orthogonal functions (EOFs) were first used in meteorology in the late 1940s. The method, which decomposes a space-time field into spatial patterns and associated time indices, contributed much in advancing our knowledge of the atmosphere. However, since the atmosphere contains all sorts of features, e.g. stationary and propagating, EOFs are unable to provide a full picture. For example, EOFs tend, in general, to be difficult to interpret because of their geometric properties, such as their global feature, and their orthogonality in space and time. To obtain more localised features, modifications, e.g. rotated EOFs (REOFs), have been introduced. At the same time, because these methods cannot deal with propagating features, since they only use spatial correlation of the field, it was necessary to use both spatial and time information in order to identify such features. Extended and complex EOFs were introduced to serve that purpose. Because of the importance of EOFs and closely related methods in atmospheric science, and because the existing reviews of the subject are slightly out of date, there seems to be a need to update our knowledge by including new developments that could not be presented in previous reviews. This review proposes to achieve precisely this goal. The basic theory of the main types of EOFs is reviewed, and a wide range of applications using various data sets are also provided. Copyright © 2007 Royal Meteorological Society [source]


Support for teenage mothers: a qualitative study into the views of women about the support they received as teenage mothers

JOURNAL OF ADVANCED NURSING, Issue 1 2001
Ank De Jonge MSc HBOV RM RGNArticle first published online: 7 JUL 200
Support for teenage mothers: a qualitative study into the views of women about the support they received as teenage mothers Aim of the study.,To gain insight into the support teenage mothers received during pregnancy, birth and their child's pre-school years and young women's perceptions of the usefulness of a support group for teenage mothers. Background.,Most qualitative studies have focused on teenage mothers around the time of the birth of their first child. For this study, women were recruited several years after the birth (median 8·5 years), so that they would have had time to reflect on the support they had received. Design.,The qualitative method of semi-structured interviews was chosen to obtain in-depth information and to allow teenage mothers' own views to be heard. Ten individual interviews and one paired interview were undertaken. Findings.,Recruitment was difficult because taking part in research was not a priority for many of the women. The study confirmed the strong link between deprivation and teenage pregnancy found in other studies, and suggested that mental health problems in teenage mothers may be more difficult to detect. Teenage women need more information on mental health and on services available to them. The fear, expressed by some of the women in this study, of becoming different from other women in their social network should be considered by health workers when establishing intervention programmes. Conclusions.,Professional bodies of health workers should lobby government to provide a minimum standard of living and sufficient child-care to combat deprivation. Former teenage mothers should be involved in the recruitment, planning and implementation stages of research and interventions. Health professionals should be aware that mental health problems in teenage mothers may be particularly difficult to detect. Key community health workers or a support group may provide information on services, mental health and education facilities available that would benefit teenage mothers. A support group may also give emotional support. [source]


Peer review in Nursing and Midwifery: a literature review

JOURNAL OF CLINICAL NURSING, Issue 4 2008
Amelia Rout MSc, BSc (Hons)
Aims and objectives., The Clinical Education Project investigated clinical education in nursing and midwifery settings. The aim of this phase was to investigate and evaluate the processes and outcomes of clinical assessment of preregistration nurses and midwives, focusing on the assessment interview, and to evaluate the feasibility of introducing peer review of the clinical assessment interview in acute clinical settings. Background., Peer review is common in many professional areas. The literature describes various applications of peer review and makes recommendations for its use. However, there is a shortage of studies investigating the use of peer review in nursing and midwifery education and practice. Design., The project involved a systematic literature review and a qualitative exploratory study. This article describes the first part of the study: a systematic literature review of peer review. The second part of the study is reported elsewhere. Methods., The systematic literature review investigated international articles written since 1994 that contained information on peer review in pre/post registration nursing and midwifery within higher education or practice. Results., From the available literature, 52 specific initiatives were analysed. The majority of articles originated in America and involved nursing staff working in secondary care settings. Fifty-one articles had missing information varying from not stating the sample size to not including information about evaluations. Conclusions., The literature review found that whilst peer review is commonplace in nursing and midwifery practice, there is a lack of robust literature about its use. Relevance to clinical practice., Peer review in clinical settings such as nursing and midwifery can facilitate the sharing of good practice and personal and professional growth. It allows participants to learn from each other and gain insight into their development. [source]


Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2006
A.-M. Shiarli
In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration , whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell. [source]


Agroecosystem modeling and optimal economic decisions: Implications for sustainable agriculture

OPTIMAL CONTROL APPLICATIONS AND METHODS, Issue 1 2008
Craig A. Bond
Abstract We adapt a biogeochemical model of an agroecosystem to account for optimal economic behavior on the part of agricultural producers. Two institutional management regimes are considered: one in which a representative producer does not account for stock pollution caused by use of agricultural inputs, and one in which the externality is internalized. Comparative statics of the steady state of the former problem are analyzed in order to gain insight into the effects of potential policy and technological changes. Results show that a more realistic ecosystem component that includes nutrient cycling can qualitatively change optimal management practices relative to a one-state representation, potentially rendering systems ,unsustainable' under some criteria and leading to policy instruments that exacerbate, rather than mitigate, external damages or the resource base. Moreover, the qualitative effect of changes in model parameters are not necessarily uniform across different agricultural systems, implying that a prescription for the so-called ,sustainable' management under one system may have unintended consequences under another system. Copyright © 2007 John Wiley & Sons, Ltd. [source]


Viruses and atypical bacteria associated with asthma exacerbations in hospitalized children,

PEDIATRIC PULMONOLOGY, Issue 6 2010
Alberto F. Maffey MD
Abstract Objectives and Working Hypothesis To evaluate the prevalence of respiratory viruses Mycoplasma pneumoniae and Chlamydophila pneumoniae and gain insight into their seasonal circulation pattern in children with acute asthma exacerbations in a temperate southern hemisphere region. Study Design Patients hospitalized between 3 months and 16 years of age were included in a 1-year prospective, observational, cross-sectional study. Respiratory secretions were collected and the presence of different viruses and atypical bacteria analyzed by immunofluorescence and polymerase chain reaction. Results Two hundred nine patients (118 females) aged (mean,±,SD) 4.4,±,4 years were included. A potential causative agent was detected in 78% of the patients. The most frequently detected viruses were respiratory syncytial virus (HRSV) (n,=,85; 40%) and rhinovirus (HRV) (n,=,52; 24.5%); M. pneumoniae and C. pneumoniae were detected in 4.5% and 2% of the cases, respectively. Patients with HRSV (vs. HRV) were hospitalized for a longer time (6.7 vs. 5.2 days, P,=,0.012), required more days of oxygen supply (5.1 vs. 3.4, P,=,0.005), had a longer duration of the exacerbation before hospitalization (3.6 vs. 1.9 days, P,=,0.001) and were younger (3.7 vs. 5.1 years, P,=,0.012). Three peaks of admissions were observed. A first peak (early autumn) caused by HRV, a second peak (winter) caused mainly by HRSV and a third one (spring), caused by HRSV, an increase in HMPV together with a second outbreak of HRV. Conclusions Children with an acute asthma exacerbation presented a high prevalence of respiratory viruses. Most hospitalizations corresponded to seasonal increases in prevalence of HRV and HRSV. Pediatr Pulmonol. 2010; 45:619,625. © 2010 Wiley-Liss, Inc. [source]


Charge carrier dissociation and recombination in polymer solar cells

PHYSICA STATUS SOLIDI (A) APPLICATIONS AND MATERIALS SCIENCE, Issue 12 2009
Carsten Deibel
Abstract In polymer:fullerene solar cells, the origin of the losses in the field-dependent photocurrent is still controversially debated. We contribute to the ongoing discussion by performing photo-induced charge extraction measurements on poly(3-hexylthiophene-2,5-diyl):[6,6]-phenyl-C61 butyric acid methyl ester solar cells in order to investigate the processes ruling charge carrier decay. Calculating the drift length of photogenerated charges, we find that polaron recombination is not limiting the photocurrent for annealed devices. Additionally, we applied Monte Carlo simulations on blends of conjugated polymer chain donors with acceptor molecules in order to gain insight into the polaron pair dissociation. The dissociation yield turns out to be rather high, with only a weak field dependence. With this complementary view on dissociation and recombination, we stress the importance of accounting for polaron pair dissociation, polaron recombination as well as charge extraction when considering the loss mechanisms in organic solar cells. [source]


Development of the vertebrate central nervous system: formation of the neural tube

PRENATAL DIAGNOSIS, Issue 4 2009
Nicholas D. E. Greene
Abstract The developmental process of neurulation involves a series of coordinated morphological events, which result in conversion of the flat neural plate into the neural tube, the primordium of the entire central nervous system (CNS). Failure of neurulation results in neural tube defects (NTDs), severe abnormalities of the CNS, which are among the commonest of congenital malformations in humans. In order to gain insight into the embryological basis of NTDs, such as spina bifida and anencephaly, it is necessary to understand the morphogenetic processes and molecular mechanisms underlying neural tube closure. The mouse is the most extensively studied mammalian experimental model for studies of neurulation, while considerable insight into underlying developmental mechanisms has also arisen from studies in other model systems, particularly birds and amphibians. We describe the process of neural tube formation, discuss the cellular mechanisms involved and highlight recent findings that provide links between molecular signaling pathways and morphogenetic tissue movements. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Fragmentation study of diastereoisomeric 2-methyltetrols, oxidation products of isoprene, as their trimethylsilyl ethers, using gas chromatography/ion trap mass spectrometry

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2004
Wu Wang
The diastereoisomeric 2-methyltetrols, 2-methylthreitol and 2-methylerythritol, were recently reported as major secondary aerosol components in natural forest aerosols and proposed as molecular markers for the photooxidation of isoprene. In this study, we examine the complex electron and methane chemical ionization behaviors of their trimethylsilyl ethers. In order to gain insight into their fragmentation behaviors, threitol and erythritol were studied as model compounds, and deuterium labeling of the trimethylsilyl groups and ion trap MS2 experiments were performed. Copyright © 2004 John Wiley & Sons, Ltd. [source]


AN ENDOGENOUS GROWTH MODEL WITH PUBLIC CAPITAL AND SUSTAINABLE GOVERNMENT DEBT,

THE JAPANESE ECONOMIC REVIEW, Issue 3 2007
ALFRED GREINER
This paper presents and analyses an endogenous growth model with public capital and public debt. It is assumed that the ratio of the primary surplus to gross domestic income is a positive linear function of the debt income ratio which assures that public debt is sustainable. The paper then derives necessary conditions for the existence of a sustainable balanced growth path for the analytical model. Further, simulations are undertaken in order to gain insight into stability properties of the model and in order to analyse growth effects of deficit financed increases in public investment. The latter is done for the model on the sustainable balanced growth path as well as for the model along the transition path. [source]


The difficulty with experience: Does practice increase susceptibility to premature closure?

THE JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS, Issue 3 2006
Kevin W. Eva PhD
Abstract Introduction: A recent review of the physician performance literature concluded that the risk of prematurely closing one's diagnostic search increases with years of experience. To minimize confounding variables and gain insight into cognitive issues relevant to continuing education, the current study was performed to test this conclusion. Methods: Physician participants were shown a series of case histories and asked to judge the probability of a pair of diagnoses. The order in which features were presented was manipulated across participants and the probabilities compared to determine the impact of information order. Two groups of participants were recruited, 1 older than and 1 younger than 60 years. Results: The probability assigned to a diagnosis tended to be greater when features consistent with that diagnosis preceded those consistent with an alternative than when the same features followed those consistent with the alternative. Older participants revealed a greater primacy effect than less experienced participants across 4 experimental conditions. Discussion: Physicians with greater experience appear to weigh their first impressions more heavily than those with less experience. Educators should design instructional activities that account for experience-specific cognitive tendencies. [source]


The structure of uracil-DNA glycosylase from Atlantic cod (Gadus morhua) reveals cold-adaptation features

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2003
Ingar Leiros
Uracil-DNA glycosylase (UDG; EC 3.2.2.3) is a DNA-repair protein that catalyses the hydrolysis of promutagenic uracil residues from single- or double-stranded DNA, generating free uracil and abasic DNA. The crystal structure of the catalytic domain of cod uracil-DNA glycosylase (cUDG) has been determined to 1.9,Å resolution, with final R factors of 18.61 and 20.57% for the working and test sets of reflections, respectively. This is the first crystal structure of a uracil-DNA glycosylase from a cold-adapted species and a detailed comparison with the human enzyme is performed in order to rationalize the cold-adapted behaviour of the cod enzyme at the structural level. The catalytic domain of cUDG comprises 223 residues, with a sequence identity to the human UDG of 75%. The tertiary structures of the two enzymes are also similar, with an overall displacement in main-chain atomic positions of 0.63,Å. The amino-acid substitutions and the differences in intramolecular hydrogen bonds, hydrophobic interactions, ion-pair interactions and electrostatic potentials are compared and discussed in order to gain insight into the factors that cause the increased activity and reduced thermostability of the cod enzyme. In particular, the reduced number of strong ion-pair interactions in the C-terminal half of cUDG is believed to greatly affect the flexibility and/or stability. Increased positive electrostatic surface potential on the DNA-facing side of cUDG seems to be responsible for increasing the affinity for the negatively charged DNA compared with that of hUDG. [source]


Crystallization and structure determination of the catalytic trimer of Methanococcus jannaschii aspartate transcarbamoylase

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2000
Jacqueline Vitali
Aspartate transcarbamoylase (ATCase) catalyzes the first step in the pyrimidine biosynthetic pathway, the reaction between carbamoyl phosphate and l -aspartate to form N -carbamoyl- l -aspartate and phosphate. The structural analysis of the ATCase catalytic trimer from Methanococcus jannaschii, a unicellular thermophilic archaeabacterium, has been undertaken in order to gain insight into the structural features that are responsible for the thermostability of the enzyme. As a first step, the catalytic trimer was crystallized in space group R32, with unit-cell parameters a = b = 265.3, c = 195.5,Å and two trimers in the asymmetric unit. Its structure was determined using molecular replacement and Patterson methods. In general, structures containing multiple copies of molecules in the asymmetric unit are difficult to determine. In this case, the two trimers in the asymmetric unit are parallel to each other and use of the Patterson function greatly simplified the structure solution. [source]


Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2009
Penchit Chitnumsub
Trypanosoma cruzi dihydrofolate reductase-thymidylate synthase (TcDHFR-TS) was crystallized in complexes with the dihydrotriazine-based or quinazoline-based antifolates C-448, cycloguanil (CYC) and Q-8 in order to gain insight into the interactions of this DHFR enzyme with classical and novel inhibitors. The TcDHFR-TS,C-448,NDP,dUMP crystal belonged to space group C2221 with two molecules per asymmetric unit and diffracted to 2.37,Å resolution. The TcDHFR-TS,CYC, TcDHFR-TS,CYC,NDP and TcDHFR-TS,Q-8,NDP crystals belonged to space group P21 with four molecules per asymmetric unit and diffracted to 2.1, 2.6 and 2.8,Å resolution, respectively. Crystals belonging to the two different space groups were suitable for structure determination. [source]


Der Census of Marine Life zieht Bilanz.

BIOLOGIE IN UNSERER ZEIT (BIUZ), Issue 4 2010
Globale "Volkszählung" unter Wasser
Abstract Ein internationales Großprojekt zur Erfassung der Vielfalt des Lebens im Meer, der Census of Marine Life, wird nach zehn Jahren in diesem Herbst mit einer großen Abschlussveranstaltung in London zu Ende gehen. Mit einer Vielzahl von Teilprojekten wurde das Leben von den tropischen Stränden über Seeberge, hydrothermale Quellen und polare Meere bis in die Tiefseebecken untersucht, um einen Überblick über die Artenvielfalt zu bekommen und Erkenntnisse darüber zu gewinnen, wie die Vielfalt des Lebens im Meer beeinflusst und gesteuert wird. Einige der Teilprojekte werden beispielhaft dargestellt, insbesondere das Projekt CeDAMar, das vom Senckenberg-Institut geleitet wird. CeDAMar erforscht die großen Tiefseebecken, die etwa die Hälfte der Erdoberfläche ausmachen und noch sehr wenig bekannt sind. Der wachsende Rohstoffbedarf rückt diesen bisher weitgehend unbeeinflussten Lebensraum in das Interesse der Industrie, und Experten von CeDAMar haben durch ihre Fachkompetenz bei der Erstellung von Richtlinien zum Schutz des Meeresbodens in internationalen Gewässern einen sehr konkreten Beitrag geleistet. Global Underwater Census , a large-scale project is taking stock The Census of Marine Life, an international large-scale project to assess the diversity of life in the ocean, will end this fall after a decade of discovery with a grand finale in London. Many so-called field projects were established to study life from tropical beaches, seamounts, hydrothermal vents, to polar seas and abyssal plains in order to get a better estimate of marine species diversity and gain insight into processes that influence the diversity of life in the oceans. Some of the field projects are presented, including the project CeDAMar under the leadership of the Senckenberg Institute. The study area of CeDAMar is abyssal plains, which comprise about half of the Earth's surface yet are very little known. Mankind's growing demand on minerals and other resources has awoken the industry's interest in a part of the ocean that so far has been relatively pristine. CeDAMar scientists have helped with their expertise to establish guidelines for the protection of the seafloor in international waters, thus demonstrating how concrete the influence of deep-sea exploration on human society can become. [source]


Nocebo as headache trigger: evidence from a sham-controlled provocation study with RF fields

ACTA NEUROLOGICA SCANDINAVICA, Issue 2008
L. J. Stovner
Background ,, A large proportion of the population in Norway has experienced headache in connection with mobile phone use, but several double-blind provocation studies with radiofrequency (RF) and sham exposures have shown no relation between headache and mobile phone RF fields. Aims ,, To investigate the type and location of headache experienced by participants in one provocation study in order to gain insight into possible causes and mechanisms of the headaches. Method ,, Questionnaire about headache, indication on figure of location of headache after exposure, interview with neurologist about headache features to make headache diagnoses. Results ,, The 17 participants went through 130 trials (sham or RF exposure). No significant difference existed in headache type, laterality or location between the headaches experienced with the two exposures types. In most participants, the headache was compatible with tension-type headache. Discussion ,, As participants experienced their typical ,mobile phone headache' both with and without RF exposure, and since the experiment did not involve the stress or the arm/head position of mobile phone use, the most likely explanation is that the headache in this situation is caused by negative expectations (nocebo). Conclusion ,, This and other similar studies indicate that headache occurring in connection with mobile phone use is not related to RF fields, and that a nocebo effect is important for this and possibly other headache triggers. [source]


Altering the Substrate Specificity of RhlI by Directed Evolution

CHEMBIOCHEM, Issue 3 2009
Pavan Kumar Reddy Kambam
Abstract Reducing virulence: RhlI catalyzes the synthesis of N -butanoyl homoserine lactone (BHL), with a minor product N -hexanoyl homoserine lactone (HHL). By using directed evolution and a genetic screen, RhlI has been engineered for enhanced production of both BHL and HHL at a similar level. Quorum sensing regulates biofilm formation and virulence factor production in the human opportunistic pathogen Pseudomonas aeruginosa. We used directed evolution to engineer RhlI, an enzyme in the RhlI,RhlR quorum-sensing system of P. aeruginosa, to alter its substrate specificity and gain insight into the molecular mechanisms of quorum sensing. By using a genetic screen, we identified a mutant with improved production of RhlI's two signaling molecules, N -butanoyl- and N -hexanoyl-homoserine lactone (BHL and HHL). In particular, production of BHL has been enhanced by more than two-fold, and the synthesis of HHL has been improved from an undetectable level to a level similar to BHL; this change indicates a significant change in substrate specificity. No significant change in the gene expression level was observed. Sequence alignments suggest that the mutations are most likely to facilitate interactions between the enzyme and the two acylated ACP substrates. This work also demonstrates that the genetic screen/selection should be useful in engineering additional quorum-sensing components. [source]


Fate of monocortical bone blocks grafted in the human maxilla: a histological and histomorphometric study

CLINICAL ORAL IMPLANTS RESEARCH, Issue 6 2003
Ilara R. Zerbo
Abstract: Local bone defects in the anterior maxilla are commonly grafted with monocortical blocks of autologous bone in order to restore the defect site prior to the placement of dental implants. Increasing evidence suggests that osteocytes are involved in the control of bone remodelling and thus may be important for optimalisation of bone structure around implants, and thus for implant osseointegration. However, it is not well known whether osteocytes will survive when bone blocks are grafted into defects. We grafted 19 patients with monocortical bone blocks derived from the symphysis, to the defect site in the maxillary alveolar process. The bone grafts were left to heal for times varying from 2.5 to 7 months. During implant installation, bone biopsies were removed using a trephine burr, and processed for hard tissue histology. Bone histology and histomorphometry were then carried out in order to gain insight into the density, viability and remodelling of the graft. Clinically, all the bone grafts were successful, with no implant failures, and little resorption was seen. Histologically, bone volume expressed as percentage of tissue volume at the implant site varied from 27% to 57% with an overall average of 41%. Bone fields with empty osteocyte lacunae were observed and measured. The amount of this so-called nonvital bone (NVB) varied between 1% and 34% of the total tissue volume. The amount of NVB decreased significantly with the time of healing. The data suggest that the majority of the osteocytes of the monocortical bone do not survive grafting. The results indicate that the NVB is progressively remodelled into new vital bone 7 months after grafting. Résumé Les lésions osseuses locales dans le maxillaire antérieur sont souvent greffées avec des blocs monocorticaux d'os autogène afin de restaurer le site avant le placement d'implants. Il semble de plus en plus évident que les ostéocytes sont induits dans le contrôle du remodelage osseux et pourraient donc être importants pour optimiser la structure osseuse autour des implants et donc l'ostéoïntégration implantaire. Cependant le taux de survie des ostéocytes lorsque les blocs osseux sont greffés dans les lésions n'est pas suffisament connu. Dix-neuf patients ont été greffés avec des blocs osseux monocorticaux provenant de la symphyse dans le site de la lésion au niveau des alvéoles maxillaires. Les greffons osseux sont restés in situ durant des périodes de 2,5 à 7 mois. Pendant l'insertion des implants des biopsies osseuses ont été prélevées avec un trépan et analysées par histologie. L'histologie osseuse et l'histomorphométrie ont été effectuées afin d'analyser la densité, la viabilité et le remodelage osseux. Cliniquement tous les greffons osseux ont été effectués avec succès sans aucun échec implantaire et peu de résorption. Histologiquement, le volume osseux exprimé en tant que pourcentage du volume tissulaire au site implantaire variait de 27 à 57 % avec une moyenne totale de 41 %. Les champs osseux avec une lacune d'ostéocytes vides ont été observés et mesurés. La quantité d'os non-vivant variait de 1 à 34 % du volume tissulaire total. La quantité d'os non-vivant diminuait significativement avec le temps de guérison. Ces données suggèrent que la majorité des ostéocytes de l'os monocortical ne survivent pas au greffage. Les résultats indiquent que l'os non-vivant est progressivement remodelé en nouvel os vivant en sept mois après le greffage. Zusammenfassung Das Schicksal von monokortikalen Knochenblöcken, welche in die menschliche Maxilla transplantiert werden: eine histologische und histomorphometrische Studie Lokale Knochendefekte in der anterioren Maxilla werden normalerweise mit monokortikalen Blöcken aus autologem Knochen aufgebaut, um den Defekt vor der Eingliederung von dentalen Implantaten aufzufüllen. Aufgrund zunehmender Evidenz wird vermutet, dass Osteozyten an der Kontrolle der Knochenremodellierung beteiligt und daher wichtig für die Optimierung der Knochenstrukturen um Implantate und für die Osseointegration der Implantate sind. Es ist jedoch nicht ausreichend bekannt, ob Osteozyten überleben, wenn Knochenblöcke in Defekte transplantiert werden. Bei 19 Patienten wurden monokortikale Knochenblöcke von der Symphyse in den Defektbereich des Alveolarfortsatzes im Oberkiefer transplantiert. Die Knochentransplantate heilten in einer Zeit zwischen 2.5 und 7 Monaten ein. Während der Implantation wurden mit einer Hohlfräse Knochenbiopsien entnommen und für die Hartgewebshistologie aufgearbeitet. Der Knochen wurde histologisch und histomorphometrisch untersucht, um Einsicht in die Dichte, Vitalität und Remodellierung des Transplantats zu erlangen. Klinisch waren alle Knochentransplantate erfolgreich eingeheilt. Es konnten keine Implantatmisserfolge gesehen werden und es traten nur geringe Resorptionen auf. Histologisch variierte das Knochenvolumen, ausgedrückt als Prozentsatz Gewebevolumen an der Implantatstelle, von 27% bis 57% mit einem Durchschnitt von 41%. Knochenfelder mit leeren Osteozytenlakunen konnten beobachtet und ausgemessen werden. Die Menge dieses sogenannten nicht-vitalen Knochens variierte zwischen 1% und 34% des totalen Gewebevolumens. Die Menge des nicht-vitalen Knochens nahm signifikant mit der Länge der Einheilzeit ab. Die Daten lassen vermuten, dass die Mehrzahl der Osteozyten des monokortikalen Knochens die Transplantation nicht überleben. Die Resultate zeigen, dass der nicht-vitale Knochen innert 7 Monaten nach der Transplantation progressiv in neuen vitalen Knochen umgebaut wird. Resumen Los defectos óseos locales en el maxilar anterior se injertan comúnmente con bloques monocorticales de hueso autólogo en orden a restaurar el lugar del defecto antes de la colocación de implantes dentales. Una creciente evidencia sugiere que los osteocitos están involucrados en el control del remodelado óseo y de este modo ser importantes para la optimalización de la estructura ósea alrededor de los implantes y así para la osteointegración de los implantes. Sin embargo, no se conoce bien si los osteocitos sobrevivirán cuando los bloques óseos sean injertados en los defectos. Hemos injertado a 19 pacientes con bloques de hueso monocortical derivados de la sínfisis al lugar del defecto en el proceso alveolar maxilar. Los injertos óseos se dejaron cicatrizar por un periodo de tiempo que varió entre 2.5 a 7 meses. Durante la implantación se tomaron biopsias óseas usando una fresa de trépano y se procesaron para histología de tejidos duros. Se llevaron a cabo entonces histología ósea e histomorfometría en orden a hacerse una idea acerca de la densidad, viabilidad y remodelado del injerto. Clínicamente, todos los injertos óseos tuvieron éxito sin fracasos de implantes y se observó poca reabsorción ósea. Histológicamente, el volumen óseo expresado como porcentaje de volumen tisular en el lugar del implante varió del 27% al 57% con una media general del 41%. Se observaron y midieron campos óseos con lagunas óseas vacías. La cantidad de hueso no vital disminuyó significativamente durante el tiempo de cicatrización. [source]


Aesthetics of Celebration, Tension and Memory: Nigeria Urban Art History

HISTORY COMPASS (ELECTRONIC), Issue 5 2008
Adérónké Adésolá Adésànyà
This essay, among other things, addresses the question of origin of Nigerian Urban art, a genre basically found in urban spaces. It highlights the various nomenclatures by which the genre has been tagged to date and provides a robust debate on the pioneer and later urban artists in the country noting the characteristics and nuances of their art. Besides establishing the character of Nigerian urban art as compelling and significant to understanding the aesthetic sensibilities and nuances of the producer culture, issues of identity, training, authorship, patronage, social memory and social responsibility, morality and immorality and how they inform, shape and complicate the creative endeavors of urban artists are brought to the fore. In this insightful interrogation of history, people and spaces one finds the emergence of a new artistic order in which Nigerian urban artists establish and expand their own idioms, unite politics with art, engage their own audiences, cultivate their own clientele, tell their own stories and that of the society, create and endorse new identities, and increasingly expand their socioeconomic space. Their creative formats essentially transform into markets where people, products and services unite. They also serve as cultural lenses through which one gain insights into class struggle in a postcolonial society and how a critical mass of the Nigerian public interprets leadership, commerce, and culture. [source]


Allelic imbalance (AI) identifies novel tissue-specific cis- regulatory variation for human UGT2B15,

HUMAN MUTATION, Issue 1 2010
Chang Sun
Abstract Allelic imbalance (AI) is a powerful tool to identify cis -regulatory variation for gene expression. UGT2B15 is an important enzyme involved in the metabolism of multiple endobiotics and xenobiotics. In this study, we measured the relative expression of two alleles at this gene by using SNP rs1902023:G>T. An excess of the G over the T allele was consistently observed in liver (P<0.001), but not in breast (P=0.06) samples, suggesting that SNPs in strong linkage disequilibrium with G253T regulate UGT2B15 expression in liver. Seven such SNPs were identified by resequencing the promoter and exon 1, which define two distinct haplotypes. Reporter gene assays confirmed that one haplotype displayed ,20% higher promoter activity compared to the other major haplotype in liver HepG2 (P<0.001), but not in breast MCF-7 (P=0.540) cells. Reporter gene assays with additional constructs pointed to rs34010522:G>T and rs35513228:C>T as the cis -regulatory variants; both SNPs were also evaluated in LNCaP and Caco-2 cells. By ChIP, we showed that the transcription factor Nrf2 binds to the region spanning rs34010522:G>T in all four cell lines. Our results provide a good example for how AI can be used to identify cis -regulatory variation and gain insights into the tissue specific regulation of gene expression. Hum Mutat 30:1,9, 2009. © 2009 Wiley-Liss, Inc. [source]


Segmenting mainland Chinese residents based on experience, intention and desire to visit Hong Kong

INTERNATIONAL JOURNAL OF TOURISM RESEARCH, Issue 4 2006
Cathy Hsu
Abstract The general consensus among marketers is that the People's Republic of China will have an enormous impact on the world's economy. However, much of this discussion is centred on China's strength as a centre of manufacturing and exports. The increase in affluence in pockets of China's 1.3 billion residents has also been the focus of firms interested in this large and virtually untapped consumer market. However, relatively little attention has been given to this market as potential sources of tourists. The purpose of this study was to profile the important visitor segments from mainland China who had previously visited, had the intention to visit or desired to visit Hong Kong,a destination traditionally priced and positioned for Western markets. Based on a sample of 470 Chinese from three cities in the mainland, the distinctive characteristics of tourists who had previously visited Hong Kong and who had strong intentions or interest to visit in the future were identified. It is hoped that this information will help tourism marketing professionals not only gain insights as to the potential of China as a source of visitors, but also highlight a useful approach to the market segmentation process. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Global Government Health Partners' Forum 2006: eighteen months later

INTERNATIONAL NURSING REVIEW, Issue 2 2010
J. Foster rn
FOSTER J., GUISINGER V., GRAHAM A., HUTCHCRAFT L. & SALMON M. (2010) Global Government Health Partners' Forum 2006: eighteen months later. International Nursing Review57, 173,179 Background:, The challenge of global health worker shortages, particularly among nurses, has been the topic of numerous forums over the last several years. Nevertheless, there has been little attention given to the roles of government chief nursing and medical officers as key partners in addressing health worker shortages. This partnership and its potential impact on the adequacy of the global health workforce was the focus of the most recent Global Government Health Partners (GGHP) Forum held in November 2006 in Atlanta, Georgia, USA. This forum was uniquely designed to create a context for government chief nursing officers and chief medical officers to engage in a joint learning and planning experience focused on positioning their leadership to impact health workforce issues. Aim:, This article describes an 18-month follow-up evaluation of the outcomes of the GGHP. The purpose of the evaluation was to assess the impact of the forum experience on the actions of participants based on the country-level plans they produced at the forum. This important feedback is intended to inform the design of future partnered global forums and gain insights into the utility of forum-based action plans. The evaluation process itself has served as an opportunity for the engagement of university faculty, students and staff in a global service learning experience. Conclusion:, The outcomes of this evaluation indicate that important progress has been made by countries whose leadership was involved in the forum, and was also an important learning activity for those participating in the conduct of the study. [source]


Do spatial effects play a role in the spatial distribution of desert-dwelling Acacia raddiana?

JOURNAL OF VEGETATION SCIENCE, Issue 4 2000
Kerstin Wiegand
Abstract. We investigated the spatial pattern of A. raddiana in the Negev desert of Israel in order to gain insights into the factors and processes driving the dynamics of this species. Using a scale-dependent measure, the ring statistic, we analysed both patterns observed in the field and time series of spatial tree distributions produced by a simulation model. In the field, random spacing was the predominant pattern observed. However seedlings were clumped on small scales. We ran the model under two contrasting scenarios representing hypotheses that explain the clumping of seedlings and the random distribution of trees. One hypothesis is that there is spatial heterogeneity in seed distribution, germination and seedling mortality, but that these heterogeneities are not correlated with each other in space. The second hypothesis assumes a correlation between these heterogeneities leading to areas suitable for establishment. However, the suitability of the sites is temporally variable. Furthermore, the second hypothesis assumes density-dependent tree mortality due to competition. Both hypotheses lead to spatial distributions that are in qualitative agreement with the patterns observed in the field. Therefore, the classical view that a clumped seedling distribution and a random pattern of older trees is due to clumped regeneration and density-dependent mortality may not hold for Acacia trees in the Negev. [source]


Structures of mannose-6-phosphate isomerase from Salmonella typhimurium bound to metal atoms and substrate: implications for catalytic mechanism

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2009
S. R. Sagurthi
Mannose-6-phosphate isomerase (MPI) catalyzes the interconversion of mannose 6-phosphate and fructose 6-phosphate. X-ray crystal structures of MPI from Salmonella typhimurium in the apo form (with no metal bound) and in the holo form (with bound Zn2+) and two other structures with yttrium bound at an inhibitory site and complexed with Zn2+ and fructose 6-phosphate (F6P) were determined in order to gain insights into the structure and the isomerization mechanism. Isomerization involves acid/base catalysis with proton transfer between the C1 and C2 atoms of the substrate. His99, Lys132, His131 and Asp270 are close to the substrate and are likely to be the residues involved in proton transfer. The interactions observed at the active site suggest that the ring-opening step is probably catalyzed by His99 and Asp270. An active-site loop consisting of residues 130,133 undergoes conformational changes upon substrate binding. Zn2+ binding induces structural order in the loop consisting of residues 50,54. The metal atom appears to play a role in substrate binding and is probably also important for maintaining the architecture of the active site. Isomerization probably follows the previously suggested cis -enediol mechanism. [source]


Loading Dependence of Self-Diffusivities of Gases in Zeolites

CHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 9 2007
R. Krishna
Abstract Experimental data on the self-diffusivities, Di,self, of a variety of gases (CH4, N2, Kr, C2H6, and C3H8) in three different zeolites, LTA, FAU, and MFI, show different dependences on the molar loading, qi. In LTA, Di,self appears to increase with qi for all molecules except N2. In FAU and in MFI the Di,self shows a sharp decrease with increasing qi. In order to gain insights into the causes behind the loading dependences, molecular dynamics (MD) simulations were carried out to determine the self-diffusivities of seven gases (CH4, N2, Kr, C2H6, C3H8, Ar, and Ne) in six different all-silica zeolite structures (MFI, AFI, FAU, CHA, DDR, and LTA). The simulation results show that the variation of Di,self with qi is determined by a variety of factors that include molecular size and shape, and degree of confinement within the zeolite. For one-dimensional channels (AFI) and intersecting channel structures (MFI), the Di,self invariably decreases with increasing qi. For zeolite structures that consist of cages separated by windows (FAU, CHA, DDR, LTA), the size of the windows is an important determinant. When the windows are wide (FAU), the Di,self decreases with qi for all molecules. If the windows are narrow (CHA, DDR and LTA), the Di,self often exhibits a sharp increase with qi, reaches a maximum and reduces to near-zero values at saturation. The sharpness with which Di,self increases with qi, is dictated by the degree of confinement at the window. Weakly confined molecules, such as Ne, do not exhibit an increase of Di,self with qi. [source]