Animal-assisted Therapy as a Pain Relief Intervention for Children

Animal-assisted therapy (AAT) is a healing modality involving a patient, an animal therapist, and handler with a goal of achieving a specified therapeutic outcome. Despite the myriad of studies documenting the benefits of AAT, no studies have yet determined the impact of animals on alleviation of pain in children. Therefore, a quasi-experimental intervention design was used to capture the change in pain and vital signs with (n = 18) or without (n = 39) AAT in children ages 3–17 in one acute care pediatric setting. The AAT intervention group experienced a significant reduction in pain level compared to the control group, t(55) = −2.86, p = .006. Although blood pressure and pulse were not impacted, respiratory rates became significantly higher in the AAT group (by an average of 2.22 breaths/min) as compared to the control group, t(55) = −2.63, p = .011. This study provides further support to the numerous health benefits of AAT, particularly for children in pain

Insights into the Mechanism of Ligand Binding to Octopine Dehydrogenase from Pecten maximus by NMR and Crystallography

Octopine dehydrogenase (OcDH) from the adductor muscle of the great scallop, Pecten maximus, catalyzes the NADH dependent, reductive condensation of L-arginine and pyruvate to octopine, NAD+, and water during escape swimming and/or subsequent recovery. The structure of OcDH was recently solved and a reaction mechanism was proposed which implied an ordered binding of NADH, L-arginine and finally pyruvate. Here, the order of substrate binding as well as the underlying conformational changes were investigated by NMR confirming the model derived from the crystal structures. Furthermore, the crystal structure of the OcDH/NADH/agmatine complex was determined which suggests a key role of the side chain of L-arginine in protein cataylsis. Thus, the order of substrate binding to OcDH as well as the molecular signals involved in octopine formation can now be described in molecular detail

Looking inside the spiky bits : a critical review and conceptualisation of entrepreneurial ecosystems

The authors wish to thank the Organisational for Economic Cooperation and Development (OECD) for funding their original research on entrepreneurial ecosystems.The concept of entrepreneurial ecosystems has quickly established itself as one of the latest ‘fads’ in entrepreneurship research. At face value, this kind of systemic approach to entrepreneurship offers a new and distinctive path for scholars and policy makers to help understand and foster growth-oriented entrepreneurship. However, its lack of specification and conceptual limitations has undoubtedly hindered our understanding of these complex organisms. Indeed, the rapid adoption of the concept has tended to overlook the heterogeneous nature of ecosystems. This paper provides a critical review and conceptualisation of the ecosystems concept: it unpacks the dynamics of the concept; outlines its theoretical limitations; measurement approaches and use in policy-making. It sets out a preliminary taxonomy of different archetypal ecosystems. The paper concludes that entrepreneurial ecosystems are a highly variegated, multi-actor and multi-scalar phenomenon, requiring bespoke policy interventions.Publisher PDFPeer reviewe

Die Lösungsstruktur des humanen GABA-A-Rezeptor-assoziierten Proteins GABARAP

The GABA$_{A}$-receptor-associated protein (GABARAP) is a member of a family of intracellular membrane trafficking and fusion proteins and has been implicated in postsynaptic membrane targeting of GABA$_{A}$ receptors and modulation of GABAergic synapses. In the hereby presented work, the first available three-dimensional solution structure of GABARAP was determined by multidimensional, heteronuclear NMR spectroscopy an isotopically $^{15}$N and $^{15}$N/$^{13}$C labeled protein. The structure is based an almost complete assignment of all $^{1}$ H, $^{15}$N and $^{13}$ C resonances and 4577 experimental proton-proton distance restraints. In the context of this work, a purification protocol for recombinant GABARAP was established. The three-dimensional fold of GABARAP is described by a four-stranded $\beta$-sheet, with two helices an either side. The $\beta$-sheet together with the two helices an the concave side of the sheet correspond to an ubiquitin-like fold. The structure of GABARAP in solution was determined in an ensemble of structures with a precision of 0.28 ± 0 .04 $\mathring{A}$ r.m.s.-deviation of the protein backbone coordinates. One part of the molecule exists in at least two different conformations that interchange with each other an a time scale between 10 and 25 Hz. Based an the special dynamical properties and topological position of IIe41, a new putative ligand-bindung site could be proposed. The structural information about GABARAP could be related to biological functions of the protein. Amino- and carboxyl-terminal ends of the protein directly interact with each other. The sidechain of Tyr115 ist integrated in a hydrophobic pocket and the hydroxyl oxygen of this tyrosine phenolic ring is hydrogen-bonded to the backbone amide nitrogen of Lys2. In contrast to the crystal structures of GABARAP and the homologous GATE-16 protein, the carboxyl terminus is an integral part of the globular and compact fold of GABARAP. Modulation of the conformation of the carboxyl-terminus might be of importance for ubiquitin-like processing and modification of the carboxyl-terminal residues. Moreover, the conformation of the carboxyl-terminus might be modulated by phosphorylation of Tyr115 or interaction with a PDZ domain containing protein, and thereby possibly regulate the function of GABARAP. Employing $^{15}$N-$^{1}$H)-HSQC titration studies, it was shown, that a part of the TM3/TM4 loop of GABA$_{A}$ receptor $_{\gamma}$2L subunit, a phage display selected peptide, and a part of the ShcB protein, interact with GABARAP wich low affinities at exactly the Same region of the molecular surface of GABARAP. The results of this work suggest that these interactions are based an formation of a pseudo-continuous $\beta$-sheet

Identification of calreticulin as ligand of GABARAP by phage display screening of a peptide library

4-Aminobutyrate type A (GABA(A)) receptor-associated protein (GABARAP) is a ubiquitin-like modifier implicated in the intracellular trafficking of GABA(A) receptors, and belongs to a family of proteins involved in intracellular vesicular transport processes, such as autophagy and intra-Golgi transport. In this article, it is demonstrated that calreticulin is a high affinity ligand of GABARAP. Calreticulin, although best known for its functions as a Ca(2+) -dependent chaperone and a Ca(2+) -buffering protein in the endoplasmic reticulum, is also localized to the cytosol and exerts a variety of extra-endoplasmic reticulum functions. By phage display screening of a randomized peptide library, peptides that specifically bind GABARAP were identified. Their amino acid sequences allowed us to identify calreticulin as a potential GABARAP binding protein. GABARAP binding to calreticulin was confirmed by pull-down experiments with brain lysate and colocalization studies in N2a cells. Calreticulin and GABARAP interact with a dissociation constant K(d) = 64 nm and a mean lifetime of the complex of 20 min. Thus, the interaction between GABARAP and calreticulin is the strongest so far reported for each protein

Structure of human immunodeficiency virus type 1 Vpr(34-51) peptide in micelle containing aqueous solution

Human immunodeficiency virus type 1 protein R (HIV-1 Vpr) promotes nuclear entry of viral nucleic acids in nondividing cells, causes G(2) cell cycle arrest and is involved in cellular differentiation and cell death. Vpr subcellular localization is as variable as its functions. It is known, that consistent with its role in nuclear transport, Vpr localizes to the nuclear envelope of human cells. Further, a reported ion channel activity of Vpr is clearly dependent on its localization in or at membranes. We focused our structural studies on the secondary structure of a peptide consisting of residues 34-51 of HIV-1 Vpr. This part of Vpr plays an important role in Vpr oligomerization, contributes to cell cycle arrest activity, and is essential for virion incorporation and binding to HHR23A, a protein involved in DNA repair. Employing NMR spectroscopy we found this part of Vpr to be almost completely alpha helical in the presence of micelles, as well as in trifluoroethanol containing and methanol/chloroform solvent. Our results provide structural data suggesting residues 34-51 of Vpr to contain an amphipathic, leucine-zipper-like alpha helix, which serves as a basis for oligomerization of Vpr and its interactions with cellular and viral factors involved in subcellular localization and virion incorporation of Vpr