349 research outputs found
The structure of an LIM-only protein 4 (LMO4) and deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4
LIM-domain only protein 4 (LMO4) is a widely expressed protein with important roles in embryonic development and breast cancer. It has been reported to bind many partners, including the transcription factor Deformed epidermal autoregulatory factor-1 (DEAF1), with which LMO4 shares many biological parallels. We used yeast two-hybrid assays to show that DEAF1 binds both LIM domains of LMO4 and that DEAF1 binds the same face on LMO4 as two other LMO4-binding partners, namely LIM domain binding protein 1 (LDB1) and C-terminal binding protein interacting protein (CtIP/RBBP8). Mutagenic screening analysed by the same method, indicates that the key residues in the interaction lie in LMO4LIM2 and the N-terminal half of the LMO4-binding domain in DEAF1. We generated a stable LMO4LIM2-DEAF1 complex and determined the solution structure of that complex. Although the LMO4-binding domain from DEAF1 is intrinsically disordered, it becomes structured on binding. The structure confirms that LDB1, CtIP and DEAF1 all bind to the same face on LMO4. LMO4 appears to form a hub in protein-protein interaction networks, linking numerous pathways within cells. Competitive binding for LMO4 therefore most likely provides a level of regulation between those different pathways.SJ was funded by an Australian Postgraduate Award (education.gov.au/australian-postgraduate-awards). JPM and JMM were awarded Senior Research
Fellowships from the Australian National and Medical Research Council (www.nhmrc.gov.au). This project was funded by an Australian Research Council (www.
arc.gov.au) Discovery Project Grant (DP110104332) to JMM and LC
Rapid descriptive consumer analysis using simultaneous and monadic sample presentation for coffee
The objective of this study was to investigate how rapid descriptive consumer analysis using simultaneous presentation of samples compared with monadic presentation of samples, using both affective and descriptive sensory evaluation methods. Simultaneous presentation of coffee samples for sensory acceptance testing, using ranking analysis, was conducted using naĂŻve assessors. In a separate session, assessors evaluated the same coffee samples, using monadic presentation and employing the same scales. Similarly, descriptive consumer analysis, using simultaneous and monadic sample presentation, was conducted using descriptive attributes chosen by the panel. For RDA (Ranking descriptive analysis), coffee samples were presented simultaneously (randomised) to assessors and subsequently ranked. The process was then repeated using the same assessors; however, samples were presented in monadic and randomised presentation order. Data accumulated from the study were analysed by Analysis of Variance (APLSR-ANOVA Partial Least Squares Regression). Results obtained indicate that simultaneous presentation of samples was more effective than monadic presentation, as a larger amount of attributes with significant (P < 0.05) intensity differences were observed using RDA. Thus, simultaneous presentation of samples also allows ranking in SAT evaluation and proved a useful tool in establishing the hedonic attributes of products. We propose to call this method Ranking Acceptance Analysis (RAA)
Elastic turbulence in curvilinear flows of polymer solutions
Following our first report (A. Groisman and V. Steinberg, \sl Nature , 53 (2000)) we present an extended account of experimental observations of
elasticity induced turbulence in three different systems: a swirling flow
between two plates, a Couette-Taylor (CT) flow between two cylinders, and a
flow in a curvilinear channel (Dean flow). All three set-ups had high ratio of
width of the region available for flow to radius of curvature of the
streamlines. The experiments were carried out with dilute solutions of high
molecular weight polyacrylamide in concentrated sugar syrups. High polymer
relaxation time and solution viscosity ensured prevalence of non-linear elastic
effects over inertial non-linearity, and development of purely elastic
instabilities at low Reynolds number (Re) in all three flows. Above the elastic
instability threshold, flows in all three systems exhibit features of developed
turbulence. Those include: (i)randomly fluctuating fluid motion excited in a
broad range of spatial and temporal scales; (ii) significant increase in the
rates of momentum and mass transfer (compared to those expected for a steady
flow with a smooth velocity profile). Phenomenology, driving mechanisms, and
parameter dependence of the elastic turbulence are compared with those of the
conventional high Re hydrodynamic turbulence in Newtonian fluids.Comment: 23 pages, 26 figure
Exclusive Photoproduction of the Cascade (Xi) Hyperons
We report on the first measurement of exclusive Xi-(1321) hyperon
photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The
final state is identified by the missing mass in p(gamma,K+ K+)X measured with
the CLAS detector at Jefferson Laboratory. We have detected a significant
number of the ground-state Xi-(1321)1/2+, and have estimated the total cross
section for its production. We have also observed the first excited state
Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss
the possibilities of a search for the recently proposed Xi5-- and Xi5+
pentaquarks.Comment: submitted to Phys. Rev.
Merkel cell carcinoma of skin-current controversies and recommendations
The review covers the current recommendations for Merkel cell carcinoma (MCC), with detailed discussion of many controversies. The 2010 AJCC staging system is more in-line with other skin malignancies although more complicated to use. The changes in staging system over time make comparison of studies difficult. A wide excision with margins of 2.5–3 cm is generally recommended. Even for primary </= 1 cm, there is a significant risk of nodal and distant metastases and hence sentinel node biopsy should be done if possible; otherwise adjuvant radiotherapy to the primary and nodal region should be given. Difficulties of setting up trials owing to the rarity of the disease and the mean age of the patient population result in infrequent reports of adjuvant or concurrent chemotherapy in the literature. The benefit, if any, is not great from published studies so far. However, there may be a subgroup of patients with high-risk features, e.g. node-positive and excellent performance status, for whom adjuvant or concurrent chemotherapy may be considered. Since local recurrence and metastases generally occur within 2 years of the initial diagnosis, patients should be followed more frequently in the first 2 years. However delayed recurrence can still occur in a small proportion of patients and long-term follow-up by a specialist is recommended provided that the general condition of the patient allows it. In summary, physician judgment in individual cases of MCC is advisable, to balance the risk of recurrence versus the complications of treatment
Contribution of DEAF1 Structural Domains to the Interaction with the Breast Cancer Oncogene LMO4
The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1
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