Geochemical evidence for widespread euxinia in the Later Cambrian ocean

Widespread anoxia in the ocean is frequently invoked as a primary driver of mass extinction as well as a long-term inhibitor of evolutionary radiation on early Earth. In recent biogeochemical studies it has been hypothesized that oxygen deficiency was widespread in subsurface water masses of later Cambrian oceans1, 2, possibly influencing evolutionary events during this time1, 2, 3. Physical evidence of widespread anoxia in Cambrian oceans has remained elusive and thus its potential relationship to the palaeontological record remains largely unexplored. Here we present sulphur isotope records from six globally distributed stratigraphic sections of later Cambrian marine rocks (about 499 million years old). We find a positive sulphur isotope excursion in phase with the Steptoean Positive Carbon Isotope Excursion (SPICE), a large and rapid excursion in the marine carbon isotope record, which is thought to be indicative of a global carbon cycle perturbation4, 5. Numerical box modelling of the paired carbon sulphur isotope data indicates that these isotope shifts reflect transient increases in the burial of organic carbon and pyrite sulphur in sediments deposited under large-scale anoxic and sulphidic (euxinic) conditions. Independently, molybdenum abundances in a coeval black shale point convincingly to the transient spread of anoxia. These results identify the SPICE interval as the best characterized ocean anoxic event in the pre-Mesozoic ocean and an extreme example of oxygen deficiency in the later Cambrian ocean. Thus, a redox structure similar to those in Proterozoic oceans6, 7, 8 may have persisted or returned in the oceans of the early Phanerozoic eon. Indeed, the environmental challenges presented by widespread anoxia may have been a prevalent if not dominant influence on animal evolution in Cambrian oceans.Organismic and Evolutionary Biolog

Earliest land plants created modern levels of atmospheric oxygen

The progressive oxygenation of the Earth’s atmosphere was pivotal to the evolution of life, but the puzzle of when and how atmospheric oxygen (O2) first approached modern levels (~21%) remains unresolved. Redox proxy data indicate the deep oceans were oxygenated during 435-392 Ma, and the appearance of fossil charcoal indicates O2>15-17% by 420-400 Ma. However, existing models have failed to predict oxygenation at this time. Here we show that the earliest plants, which colonized the land surface from ~470 Ma onwards, were responsible for this mid- Paleozoic oxygenation event, through greatly increasing global organic carbon burial – the net long-term source of O2. We use a trait-based ecophysiological model to predict that cryptogamic vegetation cover could have achieved ~30% of today’s global terrestrial net primary productivity by~445 Ma. Data from modern bryophytes suggests this plentiful early plant material had a much higher molar C:P ratio (~2000) than marine biomass (~100), such that a given weathering flux of phosphorus could support more organic carbon burial. Furthermore, recent experiments suggest that early plants selectively increased the flux of phosphorus (relative to alkalinity) weathered from rocks. Combining these effects in a model of long-term biogeochemical cycling, we reproduce a sustained +2‰ increase in the carbonate carbon isotope (δ13C) record by ~445 Ma, and predict a corresponding rise in O2 to present levels by 420-400 Ma, consistent with geochemical data. This oxygen rise represents a permanent shift in regulatory regime to one where fire-mediated negative feedbacks on organic carbon burial stabilise high O2 levels

A digital pathology tool for quantification of color features in histologic specimens.

In preclinical research, histological analysis of tissue samples is often limited to qualitative or semiquantitative scoring assessments. The reliability of this analysis can be impaired by the subjectivity of these approaches, even when read by experienced pathologists. Furthermore, the laborious nature of manual image assessments often leads to the analysis being restricted to a relatively small number of images that may not accurately represent the whole sample. Thus, there is a clear need for automated image analysis tools that can provide robust and rapid quantification of histologic samples from paraffin-embedded or cryopreserved tissues. To address this need, we have developed a color image analysis algorithm (DigiPath) to quantify distinct color features in histologic sections. We demonstrate the utility of this tool across multiple types of tissue samples and pathologic features, and compare results from our program to other quantitative approaches such as color thresholding and hand tracing. We believe this tool will enable more thorough and reliable characterization of histological samples to facilitate better rigor and reproducibility in tissue-based analyses

Nutrition Competencies in Health Professionals' Education and Training: A New Paradigm

Most health care professionals are not adequately trained to address diet and nutrition-related issues with their patients, thus missing important opportunities to ameliorate chronic diseases and improve outcomes in acute illness. In this symposium, the speakers reviewed the status of nutrition education for health care professionals in the United States, United Kingdom, and Australia. Nutrition education is not required for educating and training physicians in many countries. Nutrition education for the spectrum of health care professionals is uncoordinated, which runs contrary to the current theme of interprofessional education. The central role of competencies in guiding medical education was emphasized and the urgent need to establish competencies in nutrition-related patient care was presented. The importance of additional strategies to improve nutrition education of health care professionals was highlighted. Public health legislation such as the Patient Protection and Affordable Care Act recognizes the role of nutrition, however, to capitalize on this increasing momentum, health care professionals must be trained to deliver needed services. Thus, there is a pressing need to garner support from stakeholders to achieve this goal. Promoting a research agenda that provides outcome-based evidence on individual and public health levels is needed to improve and sustain effective interprofessional nutrition education

Archive of Darkness:William Kentridge's Black Box/Chambre Noire

Situating itself in histories of cinema and installation art, William Kentridge's Black Box/Chambre Noire (2005) raises questions about screens, exhibition space, site-specificity and spectatorship. Through his timely intervention in a debate on Germany’s colonial past, Kentridge’s postcolonial art has contributed to the recognition and remembrance of a forgotten, colonial genocide. This article argues that, by transposing his signature technique of drawings for projection onto a new set of media, Kentridge explores how and what we can know through cinematic projection in the white cube. In particular, his metaphor of the illuminated shadow enables him to animate archival fragments as shadows and silhouettes. By creating a multi-directional archive, Black Box enables an affective engagement with the spectres of colonialism and provides a forum for the calibration of moral questions around reparation, reconciliation and forgiveness

Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing

Functional coordination of alternative splicing in the mammalian central nervous system

BACKGROUND: Alternative splicing (AS) functions to expand proteomic complexity and plays numerous important roles in gene regulation. However, the extent to which AS coordinates functions in a cell and tissue type specific manner is not known. Moreover, the sequence code that underlies cell and tissue type specific regulation of AS is poorly understood. RESULTS: Using quantitative AS microarray profiling, we have identified a large number of widely expressed mouse genes that contain single or coordinated pairs of alternative exons that are spliced in a tissue regulated fashion. The majority of these AS events display differential regulation in central nervous system (CNS) tissues. Approximately half of the corresponding genes have neural specific functions and operate in common processes and interconnected pathways. Differential regulation of AS in the CNS tissues correlates strongly with a set of mostly new motifs that are predominantly located in the intron and constitutive exon sequences neighboring CNS-regulated alternative exons. Different subsets of these motifs are correlated with either increased inclusion or increased exclusion of alternative exons in CNS tissues, relative to the other profiled tissues. CONCLUSION: Our findings provide new evidence that specific cellular processes in the mammalian CNS are coordinated at the level of AS, and that a complex splicing code underlies CNS specific AS regulation. This code appears to comprise many new motifs, some of which are located in the constitutive exons neighboring regulated alternative exons. These data provide a basis for understanding the molecular mechanisms by which the tissue specific functions of widely expressed genes are coordinated at the level of AS

Trans-Atlantic application of the Baltic Middle and Upper Ordovician carbon isotope zonation

Application of the recently introduced Baltic d13C isotope zonation to a composite North American Darriwilian through Hirnantian succession shows that in most intervals there is good trans-Atlantic agreement not only between the isotope zones but also with the available biostratigraphic data. This indicates that this isotope zonation is a useful tool for improving previously uncertain long-distance correlations