The relationship between the L1 and L2 domains of the insulin and epidermal growth factor receptors and leucine-rich repeat modules

BACKGROUND: Leucine-rich repeats are one of the more common modules found in proteins. The leucine-rich repeat consensus motif is LxxLxLxxNxLxxLxxLxxLxx- where the first 11–12 residues are highly conserved and the remainder of the repeat can vary in size Leucine-rich repeat proteins have been subdivided into seven subfamilies, none of which include members of the epidermal growth factor receptor or insulin receptor families despite the similarity between the 3D structure of the L domains of the type I insulin-like growth factor receptor and some leucine-rich repeat proteins. RESULTS: Here we have used profile searches and multiple sequence alignments to identify the repeat motif Ixx-LxIxx-Nx-Lxx-Lxx-Lxx-Lxx- in the L1 and L2 domains of the insulin receptor and epidermal growth factor receptors. These analyses were aided by reference to the known three dimensional structures of the insulin-like growth factor type I receptor L domains and two members of the leucine rich repeat family, porcine ribonuclease inhibitor and internalin 1B. Pectate lyase, another beta helix protein, can also be seen to contain the sequence motif and much of the structural features characteristic of leucine-rich repeat proteins, despite the existence of major insertions in some of its repeats. CONCLUSION: Multiple sequence alignments and comparisons of the 3D structures has shown that right-handed beta helix proteins such as pectate lyase and the L domains of members of the insulin receptor and epidermal growth factor receptor families, are members of the leucine-rich repeat superfamily

Landmarks in Insulin Research

Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor

The Role of Emotional Overcontrol in Acceptance of Counselor Training Feedback

Effective feedback is a critical component of counselor training. The degree to which a recipient is able or willing to accept feedback can impact learning and skill development significantly. Recognizing individual trait differences can help the field of counseling understand feedback receptivity in counseling students. This study examined the possible relationship between feedback receptivity and the individual trait of emotional overcontrol. Results indicate that overcontrol accounted for variance in scores on a measure of feedback receptivity in a sample of counseling students, suggesting that individual trait differences meaningfully affect feedback receptivity

On the zig-zag pilot-wave approach for fermions

We consider a pilot-wave approach for the Dirac theory that was recently proposed by Colin and Wiseman. In this approach, the particles perform a zig-zag motion, due to stochastic jumps of their velocity. We respectively discuss the one-particle theory, the many-particle theory and possible extensions to quantum field theory. We also discuss the non-relativistic limit of the one-particle theory. For a single particle, the motion is always luminal, a feature that persists in the non-relativistic limit. For more than one particle the motion is in general subluminal.Comment: 23 pages, no figures, LaTe

Accountability and Transparency of Entrepreneurial Journalism: Unresolved ethical issues in crowdfunded journalism projects

Crowdfunding is a new business model in which journalists rely—and depend—on (micro-) payments by a large number of supporters to finance their reporting. In this form of entrepreneurial journalism the roles of publisher, fundraiser and journalist often overlap. This raises questions about conflicts of interest, accountability and transparency. The article presents the results of selected case studies in four different European countries—Germany (Krautreporter), Italy (Occhidellaguerra), the United Kingdom (Contributoria) and the Netherlands (De Correspondent)—as well as one US example (Kickstarter). The study used a two-step methodological approach: first a content analysis of the websites and the Twitter accounts with regard to practices of media accountability, transparency and user participation was undertaken. The aim was to investigate how far ethical challenges in crowdfunded entrepreneurial journalism are accounted for. Second, we present findings from semi-structured interviews with journalists from each crowdfunding. The study provides evidence about the ethical issues in this area, particularly in relation to production transparency and responsiveness. The study also shows that in some cases of crowdfunding (platforms), accountability is outsourced and implemented only through the audience participation

Structural Congruency of Ligand Binding to the Insulin and Insulin/Type 1 Insulin-like Growth Factor Hybrid Receptors

SummaryThe homodimeric insulin and type 1 insulin-like growth factor receptors (IR and IGF-1R) share a common architecture and each can bind all three ligands within the family: insulin and insulin-like growth factors I and II (IGF-I and IFG-II). The receptor monomers also assemble as heterodimers, the primary ligand-binding sites of which each comprise the first leucine-rich repeat domain (L1) of one receptor type and an α-chain C-terminal segment (αCT) of the second receptor type. We present here crystal structures of IGF-I bound to such a hybrid primary binding site and of a ligand-free version of an IR αCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures, refined at 3.0-Å resolution, prove congruent to respective existing structures of insulin-complexed IR310.T and the intact apo-IR ectodomain. As such, they provide key missing links in the emerging, but sparse, repertoire of structures defining the receptor family

The Roles of Extrinsic and Intrinsic Factors in the Freshwater Life-History Dynamics of a Migratory Salmonid

Key life-cycle transitions, such as metamorphosis or migration, can be altered by a variety of external factors, such as climate variation, strong species interactions, and management intervention, or modulated by density dependence. Given that these life-history transitions can influence population dynamics, understanding the simultaneous effects of intrinsic and extrinsic controls on life-history expression is particularly relevant for species of management or conservation importance. Here, we examined how life histories of steelhead (Oncorhynchus mykiss) are affected by weather, pink salmon abundance (Oncorhynchus gorbuscha), experimental nutrient addition, and density-dependent processes. We tested for impacts on the size of steelhead smolts (juveniles migrating to the sea), as well as their age and abundance across four decades in the Keogh River, British Columbia, Canada. Larger steelhead smolts were associated with warmer years and artificial nutrient addition. In addition, higher pink salmon abundance and artificial nutrient addition correlated with juvenile steelhead migrating at younger ages. While density dependence appeared to be the primary factor regulating the abundance of steelhead smolts, nutrient addition and temperature were positively and negatively associated with smolt production, respectively, prior to 1991, and pink salmon spawning abundance was positively associated with smolt production after 1990. Thus, this study provides evidence that the temporal dynamics of one species of salmon is linked to the juvenile life history of co-occurring steelhead. A complex interplay of species interactions, nutrient subsidies, density dependence, and climatic variation can control the life-history expression of species with complex life cycles

A connection between star formation activity and cosmic rays in the starburst galaxy M 82

Although Galactic cosmic rays (protons and nuclei) are widely believed to be dominantly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly a century after their discovery [1]. The active regions of starburst galaxies have exceptionally high rates of star formation, and their large size, more than 50 times the diameter of similar Galactic regions, uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density [2]. The cosmic rays produced in the formation, life, and death of their massive stars are expected to eventually produce diffuse gamma-ray emission via their interactions with interstellar gas and radiation. M 82, the prototype small starburst galaxy, is predicted to be the brightest starburst galaxy in gamma rays [3, 4]. Here we report the detection of >700 GeV gamma rays from M 82. From these data we determine a cosmic-ray density of 250 eV cm-3 in the starburst core of M 82, or about 500 times the average Galactic density. This result strongly supports that cosmic-ray acceleration is tied to star formation activity, and that supernovae and massive-star winds are the dominant accelerators.Comment: 18 pages, 4 figures; published in Nature; Version is prior to Nature's in-house style editing (differences are minimal

VERITAS Observations of the BL Lac Object 1ES 1218+304

The VERITAS collaboration reports the detection of very-high-energy (VHE) gamma-ray emission from the high-frequency-peaked BL Lac object 1ES 1218+304 located at a redshift of z=0.182. A gamma-ray signal was detected with high statistical significance for the observations taken during several months in the 2006-2007 observing season. The photon spectrum between ~160 GeV and ~1.8 TeV is well described by a power law with an index of Gamma = 3.08 +/- 0.34(stat) +/- 0.2(sys). The integral flux above 200 GeV corresponds to ~6% of that of the Crab Nebula. The light curve does not show any evidence for VHE flux variability. Using lower limits on the density of the extragalactic background light (EBL) in the near-IR to mid-IR we are able to limit the range of intrinsic energy spectra for 1ES 1218+304. We show that the intrinsic photon spectrum is harder than a power law with an index of Gamma = 2.32 +/- 0.37. When including constraints from the spectra of 1ES 1101-232 and 1ES 0229+200, the spectrum of 1ES 1218+304 is likely to be harder than Gamma = 1.86 +/- 0.37.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008