Consequences of a crystal mush-dominated magma plumbing system: a mid-ocean ridge perspective

Crystal mush is rapidly emerging as a new paradigm for the evolution of igneous systems. Mid-ocean ridges provide a unique opportunity to study mush processes: geophysical data indicate that, even at the most magmatically robust fast-spreading ridges, the magma plumbing system typically comprises crystal mush. In this paper, we describe some of the consequences of crystal mush for the evolution of the mid-ocean ridge magmatic system. One of these is that melt migration by porous flow plays an important role, in addition to rapid, channelized flow. Facilitated by both buoyancy and (deformation-enhanced) compaction, porous flow leads to reactions between the mush and migrating melts. Reactions between melt and the surrounding crystal framework are also likely to occur upon emplacement of primitive melts into the mush. Furthermore, replenishment facilitates mixing between the replenishing melt and interstitial melts of the mush. Hence, crystal mushes facilitate reaction and mixing, which leads to significant homogenization, and which may account for the geochemical systematics of mid-ocean ridge basalt (MORB). A second consequence is cryptic fractionation. At mid-ocean ridges, a plagioclase framework may already have formed when clinopyroxene saturates. As a result, clinopyroxene phenocrysts are rare, despite the fact that the vast majority of MORB records clinopyroxene fractionation. Hence, melts extracted from crystal mush may show a cryptic fractionation signature. Another consequence of a mush-dominated plumbing system is that channelized flow of melts through the crystal mush leads to the occurrence of vertical magmatic fabrics in oceanic gabbros, as well as the entrainment of diverse populations of phenocrysts. Overall, we conclude that the occurrence of crystal mush has a number of fundamental implications for the behaviour and evolution of magmatic systems, and that mid-ocean ridges can serve as a useful template for trans-crustal mush columns elsewher

The significance of plagioclase textures in mid-ocean ridge basalt (Gakkel Ridge, Arctic Ocean)

Textures and compositions of minerals can be used to infer the physiochemical conditions present within magmatic systems. Given that plagioclase is an abundant phase in many magmatic systems, understanding the link between texture and process is vital. Here, we present a database of textural and compositional data for > 1800 plagioclase crystals in mid-ocean ridge basalt from the Gakkel Ridge (Arctic Ocean) to investigate the physiochemical conditions and processes that govern the formation of plagioclase textures and compositions. The Gakkel basalts have high modal crystal contents (up to 50%). The crystal cargo is complex, with both individual plagioclase and glomerocrysts showing large variations in crystal habit, zoning and resorption. The most common types of zoning are reverse and patchy; we attribute patchy zoning to infilling following either skeletal growth or resorption. Resorption is abundant, with multiple resorption events commonly present in a single crystal, and results from both magmatic recharge and decompression. Periods of strong undercooling, distinct to quench crystallisation, are indicated by matured skeletal crystals and thin normally zoned melt inclusion-rich bands following resorption. Individual samples often contain diverse textural and compositional plagioclase groups. Furthermore, most plagioclase is not in equilibrium with its host melt. Finally, the porous open structures of some glomerocrysts suggest that they represent pieces of entrained disaggregated mush. We interpret this to indicate that the crystal cargo is not generally phenocrystic in origin. Instead, plagioclase crystals that formed in different parts of a mush-dominated plumbing system were entrained into ascending melts. The textures of individual crystals are a function of their respective histories of (under)cooling, magma mixing and decompression. The morphologies of melt inclusion trapped in the plagioclase crystals are associated with specific host crystal textures, suggesting a link between plagioclase crystallisation processes and melt inclusion entrapment. The database of plagioclase presented herein may serve as a template for the interpretation of plagioclase textures in magmatic systems elsewhere

Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice.

NBEAL2 encodes a multidomain scaffolding protein with a putative role in granule ontogeny in human platelets. Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of α-granules within blood platelets and progressive bone marrow fibrosis. We present here a novel Nbeal2(-/-) murine model of GPS and demonstrate that the lack of α-granules is due to their loss from platelets/mature megakaryocytes (MKs), and not by initial impaired formation. We show that the lack of Nbeal2 confers a proinflammatory phenotype to the bone marrow MKs, which in combination with the loss of proteins from α-granules drives the development of bone marrow fibrosis. In addition, we demonstrate that α-granule deficiency impairs platelet function beyond their purely hemostatic role and that Nbeal2 deficiency has a protective effect against cancer metastasis.This work was funded by the British Heart Foundation to CG (FS09/039) and WHO and AR (RG/09/12/28096); NHSBT to CB and HM; Wellcome Trust (WT098051) to ZM, ELC, JE, HWJ and AOS.This is the accepted manuscript. The final published version is available from Blood at http://www.bloodjournal.org/content/early/2014/09/25/blood-2014-04-566760

Metabolic analysis of the interaction between plants and herbivores

Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Has Motivational Interviewing fallen into its own Premature Focus Trap?

Since the initial conception of the behaviour change method Motivational Interviewing, there has been a shift evident in epistemological, methodological and practical applications, from an inductive, process and practitioner-focussed approach to that which is more deductive, research-outcome, and confirmatory-focussed. This paper highlights the conceptual and practical problems of adopting this approach, including the consequences of assessing the what (deductive outcome-focussed) at the expense of the how (inductively process-focussed). We encourage a return to an inductive, practitioner and client-focussed MI approach and propose the use of Computer Assisted Qualitative Data Analysis Systems such as NVivo in research initiatives to support this aim

Genome-Wide Association Study of Coronary Heart Disease and Its Risk Factors in 8,090 African Americans: The NHLBI CARe Project

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia

Bringing the Tiger Back from the Brink—The Six Percent Solution

This article does not have an abstract

Stable Mutated tau441 Transfected SH-SY5Y Cells as Screening Tool for Alzheimer’s Disease Drug Candidates

The role of hyperphosphorylation of the microtubule-associated protein tau in the pathological processes of several neurodegenerative diseases is becoming better understood. Consequently, development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. For this reason, dependable in vitro and in vivo models that reflect tau hyperphosphorylation in human diseases are needed. In this study, we generated and validated an in vitro model appropriate to test potential curative and preventive compound effects on tau phosphorylation. For this purpose, a stably transfected SH-SY5Y cell line was constructed over-expressing mutant human tau441 (SH-SY5Y-TMHT441). Analyses of expression levels and tau phosphorylation status in untreated cells confirmed relevance to human diseases. Subsequently, the effect of different established kinase inhibitors on tau phosphorylation (e.g., residues Thr231, Thr181, and Ser396) was examined. It was shown with several methods including immunosorbent assays and mass spectrometry that the phosphorylation pattern of tau in SH-SY5Y-TMHT441 cells can be reliably modulated by these compounds, specifically targeting JNK, GSK-3, CDK1/5, and CK1. These four protein kinases are known to be involved in in vivo tau phosphorylation and are therefore authentic indicators for the suitability of this new cell culture model for tauopathies

Active Trachoma and Ocular Chlamydia trachomatis Infection in Two Gambian Regions: On Course for Elimination by 2020?

Trachoma is the leading infectious cause of blindness worldwide, and is mainly found in tropical and poor countries. It is caused by infection of the eyes with the bacterium Chlamydia trachomatis. However, sometimes the clinical signs of disease can be present without infection being detected. Control efforts involve surgery, antibiotic treatment, face washing, and environmental improvement for better hygiene. Surveys of trachoma help countries to know whether and where they should implement control interventions. The Gambia is found in West Africa and has suffered from trachoma for decades. We conducted a survey of two Gambian regions to look at how much trachoma disease and C. trachomatis infection there is in the eyes. We found that although there was enough disease (≥10%) to warrant antibiotic treatment for everyone in the regions, there was nearly no infection (0.3%). This means that using clinical signs alone to make treatment decisions in low prevalence settings like The Gambia can lead to the waste of scarce resources. Our results also suggest that since less than 1% of children are infected with C. trachomatis, The Gambia is on course to achieve the World Health Organization's aim of eliminating blinding trachoma by the year 2020