bluuebunny/crossref_metadata_2025_split huggingface dataset:
Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment
Authors: Lind M. , Boman K. , Johansson L. , Nilsson T. K. , Järvholm L. Slunga , Jansson J.‐H. 
Published: June 2011

Abstract.  Lind M, Boman K, Johansson L, Nilsson TK, Slunga Järvholm L, Jansson J‐H (Address: Department of Public Health and Clinical Medicine, Umeå University; Department of Clinical Chemistry, Örebro University Hospital). Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment. J Intern Med 2012; 271: 239–246.Aims.  Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC‐treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all‐cause mortality.Methods and results.  A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow‐up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41–4.56) for major bleeding and HR 2.19 (95% CI 1.38–3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40–2.01) and all‐cause mortality (HR 1.77, 95% CI 1.52–2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high‐sensitivity C‐reactive protein and creatinine.Conclusions.  Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all‐cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.
Immunohistochemical characterization of γ‐secretase activating protein expression in Alzheimer's disease brains
Authors: Satoh J. , Tabunoki H. , Ishida T. , Saito Y. , Arima K. 
Published: June 2011

J. Satoh, H. Tabunoki, T. Ishida, Y. Saito and K. Arima (2012) Neuropathology and Applied Neurobiology38, 132–141Immunohistochemical characterization of γ‐secretase activating protein expression in Alzheimer's disease brainsAims: A recent study showed that γ‐secretase activating protein (GSAP), derived from a C‐terminal fragment of pigeon homolog (PION), increases amyloid‐β (Aβ) production by interacting with presenilin‐1 (PS1) and the β‐secretase‐cleaved C‐terminal fragment of amyloid precursor protein (APP‐CTF). In the study, knockdown of GSAP reduces production of Aβ and plaque formation in the brain of APPswe and PS1ΔE9 double transgenic mice without affecting the Notch‐dependent pathway. Therefore, GSAP is an ideal target for designing γ‐secretase modulators with least side effects in Alzheimer's disease (AD). However, at present, the precise distribution of GSAP in AD brains remains to be characterized. Methods: By immunohistochemistry, we studied GSAP expression in the frontal cortex and the hippocampus of 11 aged AD and 17 age‐matched control cases. Results: GSAP immunoreactivity exhibited distinct morphological features, such as fine granular cytoplasmic deposits, dense nodular and patchy deposits, beads and string‐like deposits, and diffuse dot‐like deposits. In both AD and control brains, a fairly small subset of cerebral cortical and hippocampal neurones expressed fine granular cytoplasmic deposits, while diffuse dot‐like deposits were more frequently found in the neuropil and neuronal processes, particularly enriched in the hippocampal CA2 and CA3 regions. Among GSAP‐immunoreactive deposits, dense nodular and patchy deposits, located in the neuropil and closely associated with PS1 expression and Aβ deposition, indicated the most distinguishing features of AD pathology. Conclusions: Aberrant regulation of GSAP expression plays a key role in acceleration of γ‐cleavage of APP‐CTF and accumulation of Aβ in AD brains.
Long‐term behavioural consequences of infant feeding: the limits of observational studies
Authors: Kramer Michael S. , Fombonne Eric , Matush Lidia , Bogdanovich Natalia , Dahhou Mourad , Platt Robert W. 
Published: June 2011

SummaryKramer MS, Fombonne E, Matush L, Bogdanovich N, Dahhou M, Platt RW. Long‐term behavioural consequences of infant feeding: the limits of observational studies. Paediatric and Perinatal Epidemiology 2011; 25: 500–506.Observational (non‐experimental) studies of the association between infant feeding and subsequent child or adult behaviour are prone to residual confounding by subtle differences in psychological attributes and interactional styles of mothers who breast feed vs. those who formula‐feed. We followed up 13 889 6.5‐year‐old Belarusian children who participated in a large cluster‐randomised trial of a breast‐feeding promotion intervention. Behaviour was evaluated using the Strengths and Difficulties Questionnaire (SDQ), completed independently by the children's parents and teachers. We compared the results of experimental (intention‐to‐treat, ITT) and observational analyses (based on feeding actually received), both adjusted for clustering. Observational analyses were additionally adjusted for geographical region, urban vs. rural residence, child's sex, age at follow‐up, birthweight, and maternal and paternal education. No differences between the randomised experimental vs. control groups were observed in ITT analyses. In contrast, small but statistically significant associations with weaning prior to 3 months were observed for parent and teacher SDQ scores on total difficulties, conduct problems and hyperactivity, even after multivariable adjustment. The absence of associations based on ITT analyses, in contrast with the significant associations based on observed breast‐feeding duration, strongly suggests that the latter are biased by residual confounding.
Resistance to liver fluke infection in the natural sheep host is correlated with a type‐1 cytokine response
Authors: PLEASANCE J. , WIEDOSARI E. , RAADSMA H. W. , MEEUSEN E. , PIEDRAFITA D. 
Published: June 2011

SummaryIndonesian thin‐tail (ITT) sheep can resist infection with Fasciola gigantica but not F. hepatica and presents an ideal model to investigate the mechanisms of liver fluke resistance in a natural host. This study examines the local and systemic immune responses of sheep during Fasciola infection and demonstrates that different anatomical tissues display distinct cytokine profiles consistent with liver fluke migration. The study also reveals a significant difference in the cytokine and antibody profiles of ITT sheep infected with F. gigantica compared with F. hepatica, with a higher ratio of IL‐4/IFN‐γ mRNA expression and specific IgG1/IgG2 antibodies strongly correlating with pathology. Interestingly, the significant type‐1 cytokine profile occurred in the lymph node closest to the site of infection at a time when the effective immune response against F. gigantica liver flukes is thought to occur. When the same F. gigantica infection in the resistant ITT sheep was compared with the susceptible Merino breed, the resistant type‐1 phenotype against liver fluke infection was only observed in the ITT sheep. These studies provide the first evidence to suggest that the induction of an early type‐1 immune response in this natural sheep host may be responsible for the ability to resist liver fluke infection.
Role of scuticociliate proteinases in infection success in turbot, Psetta maxima (L.)
Authors: PIAZZON C. , LAMAS J. , LEIRO J. M. 
Published: June 2011

SummaryScuticociliatosis caused by Philasterides dicentrarchi is one of the most severe diseases of farmed turbot, Psetta maxima (L.). Immunized fish showed elevated levels of specific antibodies (Ab), which caused the destruction of parasites through the activation of complement by the alternative and classical pathways. By using affinity chromatography on bacitracin–sepharose columns, we demonstrated the existence of high levels of parasite proteinases in the serum and, to a lesser extent, in the ascitic fluid of experimentally infected fish, and the absence of such proteinases in the serum of uninfected fish. Serum from uninfected fish displayed haemolytic activity against sheep red blood cells. However, incubation of this serum with parasite proteinases led to a decrease in serum haemolytic activity, suggesting that proteinases are able to destroy fish complement. Proteinases isolated from serum or ascitic fluid of infected fish were also able to degrade turbot Ab. Preincubation of turbot serum containing specific Ab for P. dicentrarchi with the proteinases led to a significant decrease in the killing activity of the serum. The results confirm that P. dicentrarchi proteinases in serum from infected fish may provide a mechanism for circumventing normal host immunity by inactivating the Ab and complement factors required for complement activation.
Hydrogen peroxide modulates the dynamic microtubule cytoskeleton during the defence responses to Verticillium dahliae toxins in Arabidopsis
Authors: YAO LIN‐LIN , ZHOU QUN , PEI BAO‐LEI , LI YING‐ZHANG 
Published: June 2011

ABSTRACTThe molecular mechanisms of signal transduction of plants in response to infection by Verticillium dahliae (VD) are not well understood. We previously showed that NO may act as an upstream signalling molecule to trigger the depolymerization of cortical microtubules in Arabidopsis. In the present study, we used the wild‐type, and atrbohD and atrbohF mutants of Arabidopsis to explore the mechanisms of action of H2O2 signals and the dynamic microtubule cytoskeleton in defence responses. We demonstrated that H2O2 may also act as an upstream signalling molecule to regulate cortical microtubule depolymerization. The depolymerization of the cortical microtubules played a functional role in the signalling pathway to mediate the expression of defence genes. The results indicate that H2O2 modulates the dynamic microtubule cytoskeleton to trigger the expression of defence genes against V. dahliae toxins (VD‐toxins) in Arabidopsis.
Impact of irradiance on the C allocation in the coastal marine diatom Skeletonema marinoi Sarno and Zingone*
Authors: NORICI ALESSANDRA , BAZZONI ANNA MARIA , PUGNETTI ALESSANDRA , RAVEN JOHN A. , GIORDANO MARIO 
Published: June 2011

ABSTRACTElemental stoichiometry and organic composition were investigated in an Adriatic strain of Skeletonema marinoi, cultured at 25 [low light (LL)] and 250 [high light (HL)]µmol photon m−2 s−1. Inorganic carbon acquisition, fixation and allocation, and silicic acid and orthophosphate uptake were also studied. The C : P ratio was below the Redfield ratio, especially at LL. In HL cells, N quota was halved, C quota was similar, silica quota was lower, growth rate and long‐term net primary productivity were almost doubled, relative to LL cells. The HL : LL cell quota ratios were 6 for lipid, 0.5 for protein and 0.4 for carbohydrate. Phosphoenolpyruvate carboxylase (PEPc) and glutamine synthetase (GS) activities were unaffected by the growth irradiance; phosphoenolpyruvate carboxykinase (PEPck) was 2.5‐fold more active in LL cells. This suggests that in S. marinoi, C4 photosynthesis is unlikely, PEPc is anaplerotic and PEPck may be involved in the conversion of lipid C to carbohydrates, especially in LL cells. Because about 50% of the cost for the production of an HL cell is caused by lipid biosynthesis, we propose that the preferential allocation of C to lipid at HL takes advantage of the relatively high volume‐based energy content of lipids, in an organism that reduces its size at each vegetative cell division.
Genomic clustering of cyanogenic glucoside biosynthetic genes aids their identification in Lotus japonicus and suggests the repeated evolution of this chemical defence pathway
Authors: Takos Adam M. , Knudsen Camilla , Lai Daniela , Kannangara Rubini , Mikkelsen Lisbeth , Motawia Mohammed S. , Olsen Carl E. , Sato Shusei , Tabata Satoshi , Jørgensen Kirsten , Møller Birger L. , Rook Fred 
Published: June 2011

SummaryCyanogenic glucosides are amino acid‐derived defence compounds found in a large number of vascular plants. Their hydrolysis by specific β‐glucosidases following tissue damage results in the release of hydrogen cyanide. The cyanogenesis deficient1 (cyd1) mutant of Lotus japonicus carries a partial deletion of the CYP79D3 gene, which encodes a cytochrome P450 enzyme that is responsible for the first step in cyanogenic glucoside biosynthesis. The genomic region surrounding CYP79D3 contains genes encoding the CYP736A2 protein and the UDP‐glycosyltransferase UGT85K3. In combination with CYP79D3, these genes encode the enzymes that constitute the entire pathway for cyanogenic glucoside biosynthesis. The biosynthetic genes for cyanogenic glucoside biosynthesis are also co‐localized in cassava (Manihot esculenta) and sorghum (Sorghum bicolor), but the three gene clusters show no other similarities. Although the individual enzymes encoded by the biosynthetic genes in these three plant species are related, they are not necessarily orthologous. The independent evolution of cyanogenic glucoside biosynthesis in several higher plant lineages by the repeated recruitment of members from similar gene families, such as the CYP79s, is a likely scenario.
Interplay of MYB factors in differential cell expansion, and consequences for tomato fruit development
Authors: Machemer Katja , Shaiman Oxana , Salts Yehiam , Shabtai Sara , Sobolev Irina , Belausov Eduard , Grotewold Erich , Barg Rivka 
Published: June 2011

SummaryWe previously identified SlFSM1 as an early fruit‐specific gene encoding a short protein harboring a non‐canonical SANT/MYB‐like domain. Here, we investigated the role of FSM1 during fruit development in tomato and its mode of action. By analyzing tomato plants ectopically expressing FSM1, we established that it negatively affects cell expansion, particularly of those cells with the highest potential to expand, such as those residing inner to the vascular bundles in the fruit pericarp. This function of FSM1 differs from that of the snapdragon FSM1‐like gene, RAD, which through an antagonistic activity with DIV participates in establishing floral asymmetry. Revealing an additional component of the FSM1/RAD regulatory complex, we show here that FSM1 physically interacts with FSB1, a previously uncharacterized factor harboring an atypical MYB repeat. We also demonstrate that FSB1 physically interacts with the transcription factor MYBI, a homolog of DIV. Our results show that the formation of the FSB1–MYBI complex is competed by FSM1, which recognizes in FSB1 the same region as MYBI does. Taken together, these studies expose a function for the FSM1/FSB1/MYBI complex in controlling tomato cell expansion, while revealing a mechanism by which competing MYB–MYB interactions could participate in the control of gene expression.
High‐resolution live imaging of plant growth in near physiological bright conditions using light sheet fluorescence microscopy
Authors: Maizel Alexis , von Wangenheim Daniel , Federici Fernán , Haseloff Jim , Stelzer Ernst H.K. 
Published: June 2011

SummaryMost plant growth occurs post‐embryonically and is characterized by the constant and iterative formation of new organs. Non‐invasive time‐resolved imaging of intact, fully functional organisms allows studies of the dynamics involved in shaping complex organisms. Conventional and confocal fluorescence microscopy suffer from limitations when whole living organisms are imaged at single‐cell resolution. We applied light sheet‐based fluorescence microscopy to overcome these limitations and study the dynamics of plant growth. We designed a special imaging chamber in which the plant is maintained vertically under controlled illumination with its leaves in the air and its root in the medium. We show that minimally invasive, multi‐color, three‐dimensional imaging of live Arabidopsis thaliana samples can be achieved at organ, cellular and subcellular scales over periods of time ranging from seconds to days with minimal damage to the sample. We illustrate the capabilities of the method by recording the growth of primary root tips and lateral root primordia over several hours. This allowed us to quantify the contribution of cell elongation to the early morphogenesis of lateral root primordia and uncover the diurnal growth rhythm of lateral roots. We demonstrate the applicability of our approach at varying spatial and temporal scales by following the division of plant cells as well as the movement of single endosomes in live growing root samples. This multi‐dimensional approach will have an important impact on plant developmental and cell biology and paves the way to a truly quantitative description of growth processes at several scales.
Political will for better health, a bottom‐up process
Authors: De Ceukelaire Wim , De Vos Pol , Criel Bart 
Published: June 2011

SummaryLately, different voices in the global public health community have drawn attention to the interaction between the State and civil society in the context of reducing health inequities. A rights‐based approach empowers people not only to claim their rights but also to demand accountability from the State. Lessons from history show that economic growth does not automatically have positive implications for population health. It may even be disruptive in the absence of strong stewardship and regulation by national and local public health authorities. The field research in which we have been involved over the past 20 years in the Philippines, Palestine, Cuba, and Europe confirms that organized communities and people’s organizations can effectively pressure the state into action towards realizing the right to health. Class analysis, influencing power relations, and giving the State a central role have been identified as three key strategies of relevant social movements and NGOs. More interaction between academia and civil society organizations could contribute to enhance and safeguard the societal relevance of public health researches. Our own experience made us discover that social movements and public health researchers have a lot to learn from one another.
Is routine dengue vector surveillance in central Brazil able to accurately monitor the Aedes aegypti population? Results from a pupal productivity survey
Authors: Pilger Daniel , Lenhart Audrey , Manrique‐Saide Pablo , Siqueira Joao Bosco , da Rocha Welington Tristão , Kroeger Axel 
Published: June 2011

SummaryObjective  To assess how well the Aedes aegypti infestation rapid survey, Levantamento Rapido de Indice para Aedes aegypti (LIRAa), is able to accurately estimate dengue vector densities and target the most important breeding sites in Goiania, Brazil.Methods  In February 2009, a pupal productivity survey was conducted in 2 districts of the city of Goiania, central Brazil. The results were compared to those of LIRAas conducted in the same districts during the months before and after the pupal productivity survey.Results  In the pupal productivity survey, 2 024 houses were surveyed and 2 969 water‐holding containers were inspected. Discarded small water containers most frequently contained immature Ae. aegypti. The most pupal‐productive containers were elevated water tanks, roof gutters and water holding roofs. Combined, these three containers accounted for <40% of all positive containers but produced >70% of all pupae. In the two districts where the pupal productivity survey was conducted, the house indices were 5.1 and 4.6 and the Breteau indices were 5.9 and 6.0. In contrast, the two LIRAs conducted in the same two districts resulted in an average house index of 1.5 and Breteau index of 2.5, with discarded items identified as the most frequently infested container type.Conclusion  Both the LIRAa and the pupal productivity survey identified discarded items as being most frequently infested with immature stages of Ae. aegypti, but the pupal productivity survey showed that elevated containers produced the greatest proportion of Ae. aegypti pupae (a proxy measure of adult vector density) and that the values of the Stegomyia indices were substantially underestimated by LIRAa. Although both surveys differ considerably in terms of sampling method and manpower, in the case of this study the LIRAa did not accurately identify or target the containers that were the most important to adult mosquito production.
Do poor people use poor quality providers? Evidence from the treatment of presumptive malaria in Nigeria
Authors: Onwujekwe Obinna , Hanson Kara , Uzochukwu Benjamin 
Published: June 2011

SummaryObjective  To determine the differences in the quality of treatment for presumptive malaria received by different socio‐economic status (SES) groups in Nigeria.Methods  The study was conducted in southeast Nigeria. A household survey was used to collect data on patterns of use of different providers for treatment of adult and childhood malaria. The quality of services provided by different provider types was assessed using treatment vignettes. Quality scores for the different providers were computed based on their responses to the different points raised in the vignettes. Patterns of household treatment seeking for fever were disaggregated by SES, and then weighted by quality score to indicate the overall quality‐weighted utilization by SES and the average quality of a visit by a member of each SES group. Equity ratios (poorest/least poor) provided the measure of inequity in quality‐weighted utilization of different providers.Results  In treatment of adult malaria, higher SES groups used more of public and private hospitals, while lower SES groups used more of traditional healers. In case of children, higher SES used more of healthcare centres and private hospitals and lower SES groups used more of pharmacy shops. The lowest quality of services was measured among laboratories, patent medicine dealers (PMDs), mixed goods shops and pharmacies, all of which are private. The highest scores were observed among the two types of public providers (public hospital and healthcare centres). The quality of treatment services utilised by consumers decreased as SES decreased. However, when the quantity normalized index was used this SES disparity almost disappeared. The resulting equity ratio was 0.96 for adults and 0.94 for children.Conclusion  Everybody used poor quality malaria treatment services but the poor people used providers with poor quality malaria treatment services more than others. The major driver of disparities in use of different providers by different SES was the greater number of visits of the higher SES groups, rather than the higher quality of the providers they used. Interventions should be developed to improve quality of treatment seeking behaviour and provision practices.