Transcriptional tools: Small molecules for modulating CBP KIX-dependent transcriptional activators

Previously it was demonstrated that amphipathic isoxazolidines are able to functionally replace the transcriptional activation domains of endogenous transcriptional activators. In addition, in vitro binding studies suggested that a key binding partner of these molecules is the CREB Binding Protein (CBP), more specifically the KIX domain within this protein. Here we show that CBP plays an essential role in the ability of isoxazolidine transcriptional activation domains to activate transcription in cells. Consistent with this model, isoxazolidines are able to function as competitive inhibitors of the activators MLL and Jun, both of which utilize a binding interaction with KIX to up-regulate transcription. Further, modification of the N2 side chain produced three analogs with enhanced potency against Jun-mediated transcription, although increased cytotoxicity was also observed. Collectively these small KIX-binding molecules will be useful tools for dissecting the role of the KIX domain in a variety of pathological processes. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 17–23, 2011.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78234/1/21548_ftp.pd

A guide to managing human activity on national wildlife refuges.

78 page

How parents build a case for Autism Spectrum Disorder during initial assessments: “We’re fighting a losing battle”

Integral to the diagnosis of autism spectrum disorder (ASD) is the initial assessment through which the existence of a ‘problem’ is first ascertained. Despite this, there remains limited research on this early part of the diagnostic pathway. In this paper, we utilised conversation analysis to examine relevant issues in relation to the practitioner-family interactions that take place within this initial assessment context. Our findings illustrated that parents typically first raised the possibility of the presence of an ASD diagnosis through ‘building a case’, which professionals were then able to ratify or negate. Further, we found that the assessments unfolded sequentially and clinical decisions were typically reached through a distinctive pattern of interaction. These findings have important implications for clinical practice, including for the study of ASD assessments and diagnosis

Hard Photodisintegration of a Proton Pair

We present a study of high energy photodisintegration of proton-pairs through the γ + 3He → p + p + n channel. Photon energies, Eγ , from 0.8 to 4.7 GeV were used in kinematics corresponding to a proton pair with high relative momentum and a neutron nearly at rest. The s−11 scaling of the cross section, as predicted by the constituent counting rule for two nucleon photodisintegration, was observed for the first time. The onset of the scaling is at a higher energy and the cross section is significantly lower than for deuteron (pn pair) photodisintegration. For Eγ below the scaling region, the scaled cross section was found to present a strong energy-dependent structure not observed in deuteron photodisintegration

March - forthcoming). Building bridges for collaborative digital reference between libraries and museums through an examination of reference in special collections. Journal of Academic Librarianship. Building Bridges for Collaborative Digital Reference be

ABSTRACT While a growing number of the digital reference services in libraries have become part of collaborative reference networks, other entities that serve similar information-seeking needs such as special collections and museums have not joined these networks, even though they are answering an increasing number of questions from off-site patrons via the Internet. This article examines the differences between questions asked electronically of traditional reference services and those asked of special collections services; it further explores how a better understanding of digital reference in special collections will facilitate the development of the tools and models needed to create a bridge between digital human intermediation at general academic libraries, special collections, and museums

Direct and random routing of a molecular motor protein at a DNA junction

With the aim of investigating how motor proteins negotiate DNA nanostructures, we produced test circuits based on recombination intermediates in which 1D translocation across a Holliday junction (HJ) could be assessed by subsequent triplex displacement signals on each DNA arm. Using the EcoR124I restriction-modification enzyme, a 3′–5′ double-strand DNA (dsDNA) translocase, we could show that the motor will tend to follow its translocated strand across a junction. Nonetheless, as the frequency of junction bypass events increases, the motor will occasionally jump tracks

Achieving consensus through professionalized head nods: The role of nodding in service encounters in Japan

While the interactional functions of head nodding in everyday Japanese conversation have been frequently studied, a discourse on head nodding as a professional communicative practice has yet to be explored. With the method of multimodal conversation analysis, the current study examines the role of nodding in a particular professional-client setting, namely, hair salon interactions. My interest specifically lies in the frequent occurrence of synchronized head nods during the “service-assessment sequence,” where both service provider and customer inspect and determine whether the completed work is adequate. I pursue mechanisms of synchronized head nods by revealing exactly how participants collaborate in producing a nod, and how their verbal actions may at times be designed accordingly. In doing so, the study provides insight into what consensus may look like at service encounters in Japan, and discusses how such nodding practices may contribute to a satisfactory closure of a business negotiation