Thermodynamic Model for Energy-Constrained Open-System Evolution of Crustal Magma Bodies Undergoing Simultaneous Recharge, Assimilation and Crystallization: the Magma Chamber Simulator

The Magma Chamber Simulator quantifies the impact of simultaneous recharge, assimilation and crystallization through mass and enthalpy balance in a multicomponent–multiphase (melt + solids ± fluid) composite system. As a rigorous thermodynamic model, the Magma Chamber Simulator computes phase equilibria and geochemical evolution self-consistently in resident magma, recharge magma and wallrock, all of which are connected by specified thermodynamic boundaries, to model an evolving open-system magma body. In a simulation, magma cools from its liquidus temperature, and crystals ± fluid are incrementally fractionated to a separate cumulate reservoir. Enthalpy from cooling, crystallization, and possible magma recharge heats wallrock from its initial subsolidus temperature. Assimilation begins when a critical wallrock melt volume fraction (0·04–0·12) in a range consistent with the rheology of partially molten rock systems is achieved. The mass of melt above this limit is removed from the wallrock and homogenized with the magma body melt. New equilibrium states for magma and wallrock are calculated that reflect conservation of total mass, mass of each element and enthalpy. Magma cooling and crystallization, addition of recharge magma and anatectic melt to the magma body (where appropriate), and heating and partial melting of wallrock continue until magma and wallrock reach thermal equilibrium. For each simulation step, mass and energy balance and thermodynamic assessment of phase relations provide major and trace element concentrations, isotopic characteristics, masses, and thermal constraints for all phases (melt + solids ± fluid) in the composite system. Model input includes initial compositional, thermal and mass information relevant to each subsystem, as well as solid–melt and solid–fluid partition coefficients for all phases. Magma Chamber Simulator results of an assimilation–fractional crystallization (AFC) scenario in which dioritic wallrock at 0·1 GPa contaminates high-alumina basalt are compared with results in which no assimilation occurs [fractional crystallization only (FC-only)]. Key comparisons underscore the need for multicomponent–multiphase energy-constrained thermodynamic modeling of open systems, as follows. (1) Partial melting of dioritic wallrock yields cooler silicic melt that contaminates hotter magma. Magma responds by cooling, but a pulse of crystallization, possibly expected based on thermal arguments, does not occur because assimilation suppresses crystallization by modifying the topology of multicomponent phase saturation surfaces. As a consequence, contaminated magma composition and crystallizing solids are distinct compared with the FC-only case. (2) At similar stages of evolution, contaminated melt is more voluminous (∼3·5×) than melt formed by FC-only. (3) In AFC, some trace element concentrations are lower than their FC-only counterparts at the same stage of evolution. Elements that typically behave incompatibly in mafic and intermediate magmas (e.g. La, Nd, Ba) may not be ‘enriched’ by crustal contamination, and the most ‘crustal’ isotope signatures may not correlate with the highest concentrations of such elements. (4) The proportion of an element contributed by anatectic melt to resident magma is typically different for each element, and thus the extent of mass exchange between crust and magma should be quantified using total mass rather than the mass of a single element. Based on these sometimes unexpected results, it can be argued that progress in quantifying the origin and evolution of open magmatic systems and documenting how mantle-derived magmas and the crust interact rely not only on improvements in instrumentation and generation of larger datasets, but also on continued development of computational tools that couple thermodynamic assessment of phase equilibria in multicomponent systems with energy and mass conservation

Recommendations for Effective Integration of Ethics and Responsible Conduct of Research (E/RCR) Education into Course-Based Undergraduate Research Experiences: A Meeting Report.

Advancement of the scientific enterprise relies on individuals conducting research in an ethical and responsible manner. Educating emergent scholars in the principles of ethics/responsible conduct of research (E/RCR) is therefore critical to ensuring such advancement. The recent impetus to include authentic research opportunities as part of the undergraduate curriculum, via course-based undergraduate research experiences (CUREs), has been shown to increase cognitive and noncognitive student outcomes. Because of these important benefits, CUREs are becoming more common and often constitute the first research experience for many students. However, despite the importance of E/RCR in the research process, we know of few efforts to incorporate E/RCR education into CUREs. The Ethics Network for Course-based Opportunities in Undergraduate Research (ENCOUR) was created to address this concern and promote the integration of E/RCR within CUREs in the biological sciences and related disciplines. During the inaugural ENCOUR meeting, a four-pronged approach was used to develop guidelines for the effective integration of E/RCR in CUREs. This approach included: 1) defining appropriate student learning objectives; 2) identifying relevant curriculum; 3) identifying relevant assessments; and 4) defining key aspects of professional development for CURE facilitators. Meeting outcomes, including the aforementioned E/RCR guidelines, are described herein

Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria.

Salmonella species are among the world's most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6'-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6'-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Gene expression signature of atypical breast hyperplasia and regulation by SFRP1

Background Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4–7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent risk indicators and/or precursor lesions to low grade ERα+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation. Methods In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and histologically normal benign (HNB) tissues from patients were microdissected. RNA was isolated, amplified linearly, labeled, and hybridized to whole transcriptome microarrays to determine gene expression profiles. Genes that were differentially expressed between AH and HNB were identified using a paired analysis. Gene expression signatures distinguishing AH and HNB were defined using AGNES and PAM methods. Regulation of gene networks was investigated using breast epithelial cell lines, explant cultures of normal breast tissue and mouse tissues. Results A 99-gene signature discriminated the histologically normal and AH tissues in 81% of the cases. Network analysis identified coordinated alterations in signaling through ERα, epidermal growth factor receptors, and androgen receptor which were associated with the development of both lobular and ductal AH. Decreased expression of SFRP1 was also consistently lower in AH. Knockdown of SFRP1 in 76N-Tert cells resulted altered expression of 13 genes similarly to that observed in AH. An SFRP1-regulated network was also observed in tissues from mice lacking Sfrp1. Re-expression of SFRP1 in MCF7 cells provided further support for the SFRP1-regulated network. Treatment of breast explant cultures with rSFRP1 dampened estrogen-induced progesterone receptor levels. Conclusions The alterations in gene expression were observed in both ductal and lobular AH suggesting shared underlying mechanisms predisposing to AH. Loss of SFRP1 expression is a significant regulator of AH transcriptional profiles driving previously unidentified changes affecting responses to estrogen and possibly other pathways. The gene signature and pathways provide insights into alterations contributing to AH breast lesions

Mycobacterium tuberculosis releases an antacid that remodels phagosomes

International audienc

Routine Outcomes Monitoring to Support Improving Care for Schizophrenia: Report from the VA Mental Health QUERI

In schizophrenia, treatments that improve outcomes have not been reliably disseminated. A major barrier to improving care has been a lack of routinely collected outcomes data that identify patients who are failing to improve or not receiving effective treatments. To support high quality care, the VA Mental Health QUERI used literature review, expert interviews, and a national panel process to increase consensus regarding outcomes monitoring instruments and strategies that support quality improvement. There was very good consensus in the domains of psychotic symptoms, side-effects, drugs and alcohol, depression, caregivers, vocational functioning, and community tenure. There are validated instruments and assessment strategies that are feasible for quality improvement in routine practice