A Method for Measuring Desquamation and its Use for Assessing the Effects of Some Common Exfoliants

Desquamation has been measured in the past by a counting chamber technique after corneocytes are removed from the skin surface and disaggregated in a dilute surfactant solution. However, we have found that complete corneocyte disaggregation is not always possible when these aggregates are recovered from sites where patent peeling is induced. Corneocyte counting in such instances is difficult or impossible. We have devised a method of measuring desquamation wherein the desquamating cells are determined as the total alkali-soluble protein after they are removed from the skin surface with an inert, self-hardening gel. Highly reproducible desquamation rates are obtained, characteristic of the individual subject. Using some common exfoliants, we show that pharmacologic response, observed as an increase in desquamation rate, is also an individual characteristic

Dynein and Dynactin Leverage Their Bivalent Character to Form a High-Affinity Interaction

Amanda E. Siglin is with Thomas Jefferson University, Shangjin Sun is with University of Delaware, Jeffrey K. Moore is with Washington University in Saint Louis, Sarah Tan is with UT Austin, Martin Poenie is with UT Austin, James D. Lear is with University of Pennsylvania, Tatyana Polenova is with University of Delaware, John A. Cooper is with Washington University in Saint Louis, and John C. Williams is with Thomas Jefferson University and Beckman Research Institute at City of Hope.Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC) and the dynactin p150Glued; however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10–44, is sufficient for binding p150Glued. Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, Pac11, produce significant defects in spindle positioning. Using the same methods we show residues 381 to 530 of p150Glued form a minimal fragment that binds to the dynein IC. Sedimentation equilibrium experiments indicate that these individual fragments are predominantly monomeric, but admixtures of the IC and p150Glued fragments produce a 2:2 complex. This tetrameric complex is sensitive to salt, temperature and pH, suggesting that the binding is dominated by electrostatic interactions. Finally, circular dichroism (CD) experiments indicate that the N-terminus of the IC is disordered and becomes ordered upon binding p150Glued. Taken together, the data indicate that the dynein-dynactin interaction proceeds through a disorder-to-order transition, leveraging its bivalent-bivalent character to form a high affinity, but readily reversible interaction.This work was supported in part by National Institutes of Health R21NS071166 (J.C.W.), R01GM085306 (J.C.W. & T.P.), NCRR SRR022316A (J.C.W.), GM 47337 (J.A.C.), NCRR 5P20RR017716-07 (T.P.), 5-T32-DK07705 (A.E.S) and The American Heart Association 0715196U (A.E.S). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog

Public criminologies: diverse perspectives on academia and policy

The origins of this Special Issue of Theoretical Criminology can be located in a ‘Modernizing Criminal Justice’ conference that we both attended in London in June 2002. The high-profile event was co-sponsored by John Jay College of Criminal Justice, New York, the Metropolitan Police and the FBI. Broadcasting crews were on hand to digest the plenary speeches of senior representatives of the British government, the judiciary and law enforcement agencies. It was also a highly corporate event, promoting the commercial products of global security and IT companies specializing in criminal justice ‘problem solving’. The opening session of the conference featured a slow motion replay of the 9/11 attacks on the Twin Towers with a voice-over informing the audience that the course of criminal justice had changed forever. This ‘post 9/11’ global war on crime and terrorism theme echoed throughout the plenary speeches and keynote sessions. What was striking was the relegation of the scheduled criminology workshops to the margins of the conference. This set off a discussion between us, during a coffee break, about why academic criminological knowledge was extraneous to the interests of the policy audiences brought together by this conference. And, of course, this quickly moved to discussion of whether criminologists should have a central place in such a forum. But while this is how our interest in criminology and public policy was initially sparked, we later found ourselves trying to pinpoint, more systematically, the different positions criminologists have taken on questions of their relevance and status within larger public policy debates.2 Our purposes in this introduction, and in the Special Issue that follows, are twofold. One aim is to outline a range of views that have been offered by academic criminologists on the discipline’s public status and its relationship to public policy formation and intellectual practice. A second goal is to argue the need for a diversity of ‘public criminologies’ wherein explicit value is placed on moving policies in more progressive directions. Our own point of view is that much more could be done than at present, particularly since there would seem to be broad criminological consensus about many policy issues facing us including punitive policies around the globe as well as the detrimental consequences of a range of harms and risks