The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress.

Excessive demands on the protein-folding capacity of the endoplasmic reticulum (ER) cause irremediable ER stress and contribute to cell loss in a number of cell degenerative diseases, including type 2 diabetes and neurodegeneration. The signals communicating catastrophic ER damage to the mitochondrial apoptotic machinery remain poorly understood. We used a biochemical approach to purify a cytosolic activity induced by ER stress that causes release of cytochrome c from isolated mitochondria. We discovered that the principal component of the purified pro-apoptotic activity is the proto-oncoprotein CRK (CT10-regulated kinase), an adaptor protein with no known catalytic activity. Crk(-/-) cells are strongly resistant to ER-stress-induced apoptosis. Moreover, CRK is cleaved in response to ER stress to generate an amino-terminal M(r)~14K fragment with greatly enhanced cytotoxic potential. We identified a putative BH3 (BCL2 homology 3) domain within this N-terminal CRK fragment, which sensitizes isolated mitochondria to cytochrome c release and when mutated significantly reduces the apoptotic activity of CRK in vivo. Together these results identify CRK as a pro-apoptotic protein that signals irremediable ER stress to the mitochondrial execution machinery

UTM RTT CWG Concept & Use Cases Package #2

The Concept & Use Cases Package #2: Technical Capability Level 3 document represents the collaborative research efforts between the FAA and NASA as joint members of the Unmanned Aircraft System Traffic Management (UTM) Research Transition Team (RTT). Contained in this document are the 1) Terms and Definitions, 2) Foundational Principles, 3) Concept Narratives, 4) Use Cases, 5) Operational Views, and 6) Roles and Responsibilities of actors interacting within what is considered to be encompassed by Technical Capability Level 3 UTM operating environments. The contents of Package #2 should NOT be considered established policy or construed as regulatory in nature. What is presented is meant to communicate the current, agreed upon understanding between the FAA and NASA on particular features of UTM as exemplified through use cases and concept narratives for the purposes of supporting joint NASA/Industry Demonstrations and the UTM Pilot Program. It is also meant to foster discussion and refinement of the concepts and approaches being pursued by the other RTT working groups

A Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome c during Apoptosis

AbstractThe mechanism during apoptosis by which cytochrome c is rapidly and completely released in the absence of mitochondrial swelling is uncertain. Here, we show that two distinct pathways are involved. One mediates release of cytochrome c across the outer mitochondrial membrane, and another, characterized in this study, is responsible for the redistribution of cytochrome c stored in intramitochondrial cristae. We have found that the “BH3-only” molecule tBID induces a striking remodeling of mitochondrial structure with mobilization of the cytochrome c stores (∼85%) in cristae. This reorganization does not require tBID's BH3 domain and is independent of BAK, but is inhibited by CsA. During this process, individual cristae become fused and the junctions between the cristae and the intermembrane space are opened

Unmanned Aircraft System Traffic Management (UTM) Research Transition Team (RTT) Concept Working Group - Concept & Use Cases Package #2 Addendum: Technical Capability Level 3

This document is a product of the joint NASA and FAA Research Transition Team's (RTT) Concept Working Group (CWG) as part of the UAS Traffic Management (UTM) project. The scope of the document covers Technical Capability Level (TCL) 3 of the UTM research path and presents the 1) Terms and Definitions, 2) Foundational Principles, 3) Concept Narratives, 4) Use Cases, 5) Operational Views (OVs), and 6) Roles and Responsibilities of actors interacting within a TCL3 environment. The document includes additional use cases to accompany the RTT CWG Package #2 document

Does Variability Across Events Affect Verb Learning in English, Mandarin, and Korean?

Extending new verbs is important in becoming a productive speaker of a language. Prior results show children have difficulty extending verbs when they have seen events with varied agents. This study further examines the impact of variability on verb learning and asks whether variability interacts with event complexity or differs by language. Children (aged 2 1⁄2 to 3 years) in the United States, China, Korea, and Singapore learned verbs linked to simple and complex events. Sets of events included one or three agents, and children were asked to extend the verb at test. Children learning verbs linked to simple movements performed similarly across conditions. However, children learning verbs linked to events with multiple objects were less successful if those events were enacted by multiple agents. A follow-up study rules out an influence of event order. Overall, similar patterns of results emerged across languages, suggesting common cognitive processes support children’s verb learning

Governing culture: legislators, interpreters and accountants

Cultural policy has become dominated by questions of how to account for the intangible value of government investments. This is as a result of longstanding developments within government’s approaches to policy making, most notably those influenced by practices of audit and accounting. This paper will outline these developments with reference to Peter Miller’s concept of calculative practices, and will argue two central points: first, that there are practical solutions to the problem of measuring the value of culture that connect central government discourses with the discourses of the cultural sector; and second, the paper will demonstrate how academic work has been central to this area of policy making. As a result of the centrality of accounting academics in cultural policy, for example in providing advice on the appropriate measurement tools and techniques, questions are raised about the role academia might take vis-à-vis public policy. Accounting professionals and academics not only provide technical expertise that informs state calculative practices, but also play a surveillance role through the audit and evaluation of government programmes, and act as interpreters in defining terms of performance measurement, success and failure. The paper therefore concludes by reflecting on recent work by Phillip Schlesinger to preserve academic integrity whilst allowing accounting scholars and academics influence and partnership in policy

Near or far: the effect of spatial distance and vocabulary knowledge on word learning

The current study investigated the role of spatial distance in word learning. Two-year-old children saw three novel objects named while the objects were either in close proximity to each other or spatially separated. Children were then tested on their retention for the name-object associations. Keeping the objects spatially separated from each other during naming was associated with increased retention for children with larger vocabularies. Children with a lower vocabulary size demonstrated better retention if they saw objects in close proximity to each other during naming. This demonstrates that keeping a clear view of objects during naming improves word learning for children who have already learned many words, but keeping objects within close proximal range is better for children at earlier stages of vocabulary acquisition. The effect of distance is therefore not equal across varying vocabulary sizes. The influences of visual crowding, cognitive load, and vocabulary size on word learning are discussed

Plasticity may change inputs as well as processes, structures, and responses

Significant work has documented neuroplasticity in development, demonstrating that developmental pathways are shaped by experience. Plasticity is often discussed in terms of the results of differences in input; differences in brain structures, processes, or responses reflect differences in experience. In this paper, I discuss how developmental plasticity also effectively changes input into the system. That is, structures and processes change in response to input, and those changed structures and processes influence future inputs. For example, plasticity may change the pattern of eye movements to a stimulus, thereby changing which part of the scene becomes the input. Thus, plasticity is not only seen in the structures and processes that result from differences in experience, but also is seen in the changes in the input as those structures and processes adapt. The systematic study of the nature of experience, and how differences in experience shape learning, can contribute to our understanding of neuroplasticity in general

Forward-Backward Asymmetry in Top Quark Production in ppbar Collisions at sqrt{s}=1.96 TeV

Reconstructable final state kinematics and charge assignment in the reaction ppbar->ttbar allows tests of discrete strong interaction symmetries at high energy. We define frame dependent forward-backward asymmetries for the outgoing top quark in both the ppbar and ttbar rest frames, correct for experimental distortions, and derive values at the parton-level. Using 1.9/fb of ppbar collisions at sqrt{s}=1.96 TeV recorded with the CDF II detector at the Fermilab Tevatron, we measure forward-backward top quark production asymmetries in the ppbar and ttbar rest frames of A_{FB,pp} = 0.17 +- 0.08 and A_{FB,tt} = 0.24 +- 0.14.Comment: 7 pages, 2 figures, submitted to Phys.Rev.Lett, corrected references and change of tex