Genomic data: building blocks for life or abstract art?

The genes found in the genetic code (genome) are sometimes called the “building blocks for life” but knowing how they impact human health can be more complicated than it sounds. This article aims to show how difficult it can be to understand how our genes can affect our health, and why it is not always easy to work out a patient’s result from genetic tests. We follow the story of Ben, whose muscles have been getting weaker for a few years. To find out why, Ben has had his genetic code sequenced, and we will walk you through a process by which his results can be analyzed. Through this activity, we will show you that analyzing patients’ genome tests is a bit like interpreting abstract art, in which different people might see and value different things

Eosinophil Secretion of Granule-Derived Cytokines

Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration, and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here, we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines

Slow roll inflation in the presence of a dark energy coupling

In models of coupled dark energy, in which a dark energy scalar field couples to other matter components, it is natural to expect a coupling to the inflaton as well. We explore the consequences of such a coupling in the context of single-field slow-roll inflation. Assuming an exponential potential for the quintessence field we show that the coupling to the inflaton causes the quintessence field to be attracted toward the minimum of the effective potential. If the coupling is large enough, the field is heavy and is located at the minimum. We show how this affects the expansion rate and the slow-roll of the inflaton field, and therefore the primordial perturbations generated during inflation. We further show that the coupling has an important impact on the processes of reheating and preheating

Education and Outreach in the Life Sciences: Qualitative Analysis Report

The DOE's National Nuclear Security Agency (NNSA) asked Pacific Northwest National Laboratory (PNNL) to consider the role of individual scientists in upholding safety and security. The views of scientists were identified as being a critical component of this policy process. Therefore, scientists, managers, and representatives of Institutional Biosafety Committees (IBCs) at the national labs were invited to participate in a brief survey and a set of focus groups. In addition, three focus groups were conducted with scientists, managers, and IBC representatives to discuss some of the questions related to education, outreach, and codes of conduct in further detail and gather additional input on biosecurity and dual-use awareness at the laboratories. The overall purpose of this process was to identify concerns related to these topics and to gather suggestions for creating an environment where both the scientific enterprise and national security are enhanced

Taking shortcuts: Cognitive conflict during motivated rule-breaking

Deliberate rule violations have typically been addressed from a motivational perspective that asked whether or not agents decide to violate rules based on contextual factors and moral considerations. Here we complement motivational approaches by providing a cognitive perspective on the processes that operate during the act of committing an unsolicited rule violation. Participants were tested in a task that allowed for violating traffic rules by exploiting forbidden shortcuts in a virtual city maze. Results yielded evidence for sustained cognitive conflict that affected performance from right before a violation throughout actually committing the violation. These findings open up a new theoretical perspective on violation behavior that focuses on processes occurring right at the moment a rule violation takes place

Taking shortcuts: Cognitive conflict during motivated rule-breaking

Deliberate rule violations have typically been addressed from a motivational perspective that asked whether or not agents decide to violate rules based on contextual factors and moral considerations. Here we complement motivational approaches by providing a cognitive perspective on the processes that operate during the act of committing an unsolicited rule violation. Participants were tested in a task that allowed for violating traffic rules by exploiting forbidden shortcuts in a virtual city maze. Results yielded evidence for sustained cognitive conflict that affected performance from right before a violation throughout actually committing the violation. These findings open up a new theoretical perspective on violation behavior that focuses on processes occurring right at the moment a rule violation takes place

Identification of Existing Surface Water Quality Monitoring Programs, Upper Illinois River Basin

published or submitted for publicationis peer reviewedOpe

A Gel-Based Dual Antibody Capture and Detection Method for Assaying of Extracellular Cytokine Secretion: EliCell

A distinguishing feature of eosinophils is their ability to rapidly release preformed cytokines from intracellular pools. Cytokines are delivered to the cell surface from granule stores by transport vesicles and are released in small packets at discrete locations along the cell surface through a process termed “piecemeal” degranulation. The study of this process has been hindered by lack of an assay sensitive enough to register minute protein concentrations and the inability to visualize morphology of cytokine secreting cells. These hindrances have necessitated our development of the EliCell assay, an agarose-based dual cytokine capture and detection system through which cytokine secretion and cellular morphology may be analyzed in concert. Cells are embedded within capture antibody-containing agarose and stimulated under conditions of interest. Extracellularly released cytokine is captured within the matrix at the point of release from the cell and can be labeled with a fluorochrome-conjugated antibody. Cytokine release and cellular morphology are visualized in parallel by phase contrast and fluorescence microscopy, respectively

An Engineered IFNγ-Antibody Fusion Protein with Improved Tumor-Homing Properties

Interferon-gamma (IFNγ) is one of the central cytokines produced by the innate and adaptive immune systems. IFNγ directly favors tumor growth control by enhancing the immunogenicity of tumor cells, induces IP-10 secretion facilitating (CXCR3+) immune cell infiltration, and can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that the targeted delivery of IFNγ to neoplastic lesions may be limited by the trapping of IFNγ-based products by cognate receptors found in different organs. Here we describe a novel fusion protein consisting of the L19 antibody, specific to the alternatively spliced extra-domain B of fibronectin (EDB), fused to a variant of IFNγ with reduced affinity to its cognate receptor. The product (named L19-IFNγ KRG) selectively localized to tumors in mice, showed favorable pharmacokinetic profiles in monkeys and regained biological activity upon antigen binding. The fusion protein was investigated in two murine models of cancer, both as monotherapy and in combination with therapeutic modalities which are frequently used for cancer therapy. L19-IFNγ KRG induced tumor growth retardation and increased the intratumoral concentration of T cells and NK cells in combination with anti-PD-1