11β-hydroxysteroid dehydrogenase type 1 has no effect on survival during experimental malaria but affects parasitemia in a parasite strain-specific manner

status: publishe

Molybdenum and Phosphorus Interact to Constrain Asymbiotic Nitrogen Fixation in Tropical Forests

Biological di-nitrogen fixation (N2) is the dominant natural source of new nitrogen to land ecosystems. Phosphorus (P) is thought to limit N2 fixation in many tropical soils, yet both molybdenum (Mo) and P are crucial for the nitrogenase reaction (which catalyzes N2 conversion to ammonia) and cell growth. We have limited understanding of how and when fixation is constrained by these nutrients in nature. Here we show in tropical forests of lowland Panama that the limiting element on asymbiotic N2 fixation shifts along a broad landscape gradient in soil P, where Mo limits fixation in P-rich soils while Mo and P co-limit in P-poor soils. In no circumstance did P alone limit fixation. We provide and experimentally test a mechanism that explains how Mo and P can interact to constrain asymbiotic N2 fixation. Fixation is uniformly favored in surface organic soil horizons - a niche characterized by exceedingly low levels of available Mo relative to P. We show that soil organic matter acts to reduce molybdate over phosphate bioavailability, which, in turn, promotes Mo limitation in sites where P is sufficient. Our findings show that asymbiotic N2 fixation is constrained by the relative availability and dynamics of Mo and P in soils. This conceptual framework can explain shifts in limitation status across broad landscape gradients in soil fertility and implies that fixation depends on Mo and P in ways that are more complex than previously thought

Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation

Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12±1 g day−1) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20 : 4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20 : 4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils

3D modelling of the flow of self-compacting concrete with or without steel fibres. Part I: slump flow test

In part I of this two-part paper, a three-dimensional Lagrangian smooth particle hydrodynamics method has been used to model the flow of self-compacting concrete (SCC) with or without short steel fibres in the slump cone test. The constitutive behaviour of this non-Newtonian viscous fluid is described by a Bingham-type model. The 3D simulation of SCC without fibres is focused on the distribution of large aggregates (larger than or equal to 8 mm) during the flow. The simulation of self-compacting high- and ultra-high- performance concrete containing short steel fibres is focused on the distribution of fibres and their orientation during the flow. The simulation results show that the fibres and/or heavier aggregates do not precipitate but remain homogeneously distributed in the mix throughout the flow

Research Trends in Evidence-Based Medicine: A Joinpoint Regression Analysis of More than 50 Years of Publication Data

Background Evidence-based medicine (EBM) has developed as the dominant paradigm of assessment of evidence that is used in clinical practice. Since its development, EBM has been applied to integrate the best available research into diagnosis and treatment with the purpose of improving patient care. In the EBM era, a hierarchy of evidence has been proposed, including various types of research methods, such as meta-analysis (MA), systematic review (SRV), randomized controlled trial (RCT), case report (CR), practice guideline (PGL), and so on. Although there are numerous studies examining the impact and importance of specific cases of EBM in clinical practice, there is a lack of research quantitatively measuring publication trends in the growth and development of EBM. Therefore, a bibliometric analysis was constructed to determine the scientific productivity of EBM research over decades. Methods NCBI PubMed database was used to search, retrieve and classify publications according to research method and year of publication. Joinpoint regression analysis was undertaken to analyze trends in research productivity and the prevalence of individual research methods. Findings Analysis indicates that MA and SRV, which are classified as the highest ranking of evidence in the EBM, accounted for a relatively small but auspicious number of publications. For most research methods, the annual percent change (APC) indicates a consistent increase in publication frequency. MA, SRV and RCT show the highest rate of publication growth in the past twenty years. Only controlled clinical trials (CCT) shows a non-significant reduction in publications over the past ten years. Conclusions Higher quality research methods, such as MA, SRV and RCT, are showing continuous publication growth, which suggests an acknowledgement of the value of these methods. This study provides the first quantitative assessment of research method publication trends in EBM

Loss of c-Cbl E3 ubiquitin ligase activity enhances the development of myeloid leukemia in FLT3-ITD mutant mice

Mutations in the FLT3 receptor tyrosine kinase (RTK) occur frequently in acute myeloid leukemia (AML), with the most common involving internal tandem duplication (ITD) within the juxtamembrane domain. FLT3-ITD mutations result in a mislocalized and constitutively activated receptor, which aberrantly phosphorylates STAT5 and upregulates the expression of its target genes. c-Cbl is an E3 ubiquitin ligase that negatively regulates RTKs, including FLT3, but whether it can downregulate mislocalized FLT3-ITD remains to be resolved. To help clarify this we combined a FLT3-ITD mutation with a loss-of-function mutation in the RING finger domain of c-Cbl that abolishes its E3 ligase activity. Mice transplanted with hematopoietic stem cells expressing both mutations rapidly develop myeloid leukemia indicating strong cooperation between the two. Although the c-Cbl mutation was shown to cause hyper-activation of another RTK, c-Kit, it had no effect on enhancing FLT3-ITD protein levels or STAT5 activation. This indicates that c-Cbl does not downregulate FLT3-ITD, and that the leukemia is driven by independent pathways involving FLT3-ITD's activation of STAT5 and mutant c-Cbl's activation of other RTKs, such as c-Kit. This study highlights the importance of c-Cbl's negative regulation of wild-type RTKs in suppressing FLT3-ITD-driven myeloid leukemi

Encouraging Vietnamese-American Women to Obtain Pap Tests Through Lay Health Worker Outreach and Media Education

BACKGROUND: Five times more Vietnamese-American women develop cervical cancer than white women. Few studies have examined whether community-based participatory research can effectively address Asian immigrants' health problems. This article reports the preliminary evaluation of 1 such project. METHODS: A coalition of 11 organizations in Santa Clara County, California worked with university researchers to design and simultaneously implement a media education (ME) campaign and a lay health worker outreach (LHWO) program to increase Vietnamese-American women's cervical cancer awareness, knowledge, and screening. Two agencies each recruited 10 lay health workers (LHWs), who, in turn, each recruited 20 women who were then randomized into 2 groups: 10 to LHWO+ME (n = 200) and 10 to ME alone (n = 200). LHWs organized meetings with women to increase their knowledge and to motivate them to obtain Pap tests. Participants completed pre- and post-intervention questionnaires. RESULTS: At post-intervention, significantly more LHWO+ME women understood that human papillomavirus and smoking cause cervical cancer. The number of women who had obtained a Pap test increased significantly among women in both LHWO+ME and ME groups, but substantially more in the LHWO+ME group. Significantly more LHWO+ME women said they intended to have a Pap test. CONCLUSIONS: Media education campaigns can increase Vietnamese women's awareness of the importance of Pap tests, but lay health workers are more effective at encouraging women to actually obtain the tests. Lay health workers are effective because they use their cultural knowledge and social networks to create change. Researchers, community members, and community-based organizations can share expert knowledge and skills, and build one another's capacities