Using an affinity resin and photoaffinity label based on phospholipid analogs of inositol 1,3,4,5-tetrakisphosphate (InsP 4 ), we have isolated, characterized, and cloned a 46-kDa protein from rat brain, which we have named centaurin-␣. Binding specificity was determined using displacement of 1-O- Receptor-stimulated phosphoinositide (PI) 1 metabolism generates numerous inositol polyphosphates (InsP n s) and inositol phospholipids, many of which may function as potential second messengers (1). Of the possible PI metabolites, Ins(1,4,5)P 3 (InsP 3 ) and diacylglycerol (DAG) are the best characterized second messengers. Generated by receptor-stimulated phospholipase C, hydrolysis of PtdIns(4,5)P 2 (2), Ins(1,4,5)P 3 binds to and gates an InsP 3 receptor calcium channel on the endoplasmic reticulum (2, 3). The lipid DAG remains in the membrane where it activates several protein kinase C isoforms and may regulate other targets (4, 5). In the membrane, DAG is metabolized rapidly to monoacylglycerol and to several phospholipids. In the cytoplasm, Ins(1,4,5)P 3 can be phosphorylated to Ins(1,3,4,5)P 4 by an InsP 3 3-kinase. Other isomers of InsP 4 , InsP 5 , and InsP 6 , some of which are synthesized independently of Ins(1,4,5)P 3 , have been identified (for review, see Ref. 6), and their production may also be regulated by receptors or during cell growth. Information from receptor binding studies, using radioactive InsP 4 and InsP 6 , have demonstrated that a number of important regulatory proteins contain high affinity InsP n binding sites. InsP n s have been implicated in the regulation of clathrin assembly proteins AP-2 (7, 8), AP-3 (9), the non-clathrin-associated coatomer proteins (10), synaptotagmin (11), and the regulation of the small GTPases ras and/or rap via a specific GTPase-activating protein (GAP) activity (12). Inositol phospholipids have also been postulated as messenger molecules. From in vivo, genetic, and permeabilized cell studies, evidence for critical roles for the inositol phospholipids PtdIns(3)P, PtdIns(4)P, and PtdIns(4,5)P 2 as regulators of membrane vesicle trafficking and cytoskeletal rearrangements is accumulating rapidly (5, 13-15). One inositol phospholipid, PtdIns(3,4,5)P 3 , has emerged as a potential messenger molecule in receptor-stimulated cells (16 -18). Synthesized by receptor-stimulated PI 3-kinase phosphorylation of PtdIns(4,5)P 2 (18), PtdInsP 3 is not a substrate for PI-specific phospholipase * This work was supported in part by National Institutes of Mental Health Grants R29MH50102 and DDRC P50HD32901 (to A. B. T.). Work at Stony Brook was supported by National Institutes of Health Grant NS29632 (to G. D. P.). The first two authors contributed equally to this study. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.The nucleotide sequence(s) reported in this paper has been submitted to the GenBank § §...

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.

This essay compares the approaches that scientific societies in the ACCESS meta-organization use to implement and assess travel award programs for URM trainees and presents a set of recommendations, including both short- and long-term outcomes assessment in populations of interest and specialized programmatic activities coupled to travel award programs.

Promoting diversity and inclusiveness in the STEM academic workforce remains a key challenge and national priority. Scientific societies can play a significant role in this process through the creation and implementation of programs to foster STEM academic workforce diversification, and by providing mentoring and skills development training that empower scientists from under-represented minority (URM) backgrounds to succeed in their communities of practice. In this article, we provide examples of challenges met by scientific societies in these areas and present data from the American Society for Cell Biology, highlighting the benefits received by trainees through long-term engagement with its programs. The success of these initiatives illustrates the impact of discipline-specific programming by scientific societies in supporting the development of URM scientists and an increasingly diverse and inclusive academic STEM community.

The tyrosine phosphatase SHP-2 has been implicated in a variety of signaling pathways, including those mediated by neurotrophins in neurons. To examine the role of SHP-2 in the development of sympathetic neurons, we inhibited the function of SHP-2 in transgenic mice by overexpressing a catalytically inactive SHP-2 mutant under the control of the human dopamine beta-hydroxylase promoter. Expression of mutant SHP-2 did not influence the survival, axon initiation, or pathfinding abilities of the sympathetic neurons. However, mutant SHP-2 expression resulted in an overproduction of sympathetic fibers in sympathetic target organs. This was due to interference with SHP-2 function, as overexpression of wild type SHP-2 had no such effect. In vitro, NGF-dependent neurite growth was inhibited in neurons expressing mutant SHP-2 but not in those expressing wild type SHP-2. Mutant (but not wt) SHP-2 expression also inhibited NGF-stimulated ERK activation. The NGF-dependent survival pathway was less affected than the neurite growth pathway. Our results suggest that NGF-regulated axon growth signals, and to a lesser degree survival signals, are mediated through a SHP-2-dependent pathway in sympathetic neurons. The increased sympathetic innervation in target tissues of neurons expressing mutant SHP-2 may result from interference with normal "stop" signals dependent on signaling by gradients of NGF.

The Inclusive Environments and Metrics in Biology Education and Research (iEMBER) network is a newly forming national community of practice that engages diversity, equity, and inclusion stakeholders in interdisciplinary collaborative projects. iEMBER was initiated with incubator funding from the National Science Foundation program for Research Coordination Networks in Undergraduate Biology Education. In June 2017, biology education researchers, social scientists, biologists, and program and policy administrators, all with interests in diversity, equity, and inclusion, met to lay the foundation for the iEMBER network. iEMBER provides a distinct forum to coordinate efforts through networking, professional development, and the initiation of collaborative research. iEMBER advances science, technology, engineering, and mathematics reform focused on diversity, equity, and inclusion through the initiation of research teams at the iEMBER biennial conference and outreach efforts at discipline-specific meetings and conferences. The focus of iEMBER is on understanding how to create inclusive, supportive, and engaging environments to foster the success of all biology students and trainees. This report focuses on the structure of the iEMBER network, two takeaways that emerged from the 2017 conference (interdisciplinary networking/collaboration and intradisciplinary broadening participation strategies), and ways for prospective members to engage in ongoing dialogue and future events. Learn more at http://iember.org .

ABSTRACTPromoting diversity and inclusiveness in the STEM academic workforce remains a key challenge and national priority. Scientific societies can play a significant role in this process through the creation and implementation of programs to foster STEM academic workforce diversification, and by providing mentoring and skills development training that empower scientists from under-represented minority (URM) backgrounds to succeed in their communities of practice. In this article, we provide examples of challenges met by scientific societies in these areas and present data from the American Society for Cell Biology, highlighting the benefits received by trainees through long-term engagement with its programs. The success of these initiatives illustrates the impact of discipline-specific programming by scientific societies in supporting the development of URM scientists and an increasingly diverse and inclusive academic STEM community.

The design of programs in support of a strong, diverse, and inclusive scientific workforce and academe requires numerous difficult conversations about sensitive topics such as the challenges scientists can face in their professional development. Theatre can be an interactive and effective way to foster discussion around such subjects. This article examines the implementation and benefits of such interactive strategies in different contexts, including the benefits of getting early career academics and professionals talking about some of the situations that women and underrepresented minorities face in the workplace, while allowing more seasoned professionals and colleagues to join in the conversation.