Five Minute Dog Feeder

In this article, the author explores music education counterforces, examining whether and how (a) federal and state education policies can better address the in-service needs of special area teachers, particularly music teachers, in the school setting; and (b) policy organizations in the music education profession (i.e., The National Association for Music Education, the National Association of Schools of Music, the College Music Society, the Society for Music Teacher Education, and the Music Education Research Council) might also address the inherent tensions between music education and schooling.     

Studies on the skull of the Indian sisorid catfish, Erethistes pussilus

The skull of Erethistes pussilus is described in detail. The general disposition of the bones corresponds to the siluroid pattern. Among the siluroid fishes, E. pussilus approaches the advanced forms in certain features such as obliteration of myodomic space, edentulous palate, absence of entopterygoids and supratemporals, intimate sutural articulation of posttemporals and complex vertebra with the cranium, diminished cranial cavity and loss of sutural articulation among the palatopterygoquadrate elements. In certain characters like the hyomandibula exclusively supported from the sphenotic, solitary hypohyal on each hyoid cornu, absence of interhyals, reduced orbits, edentulous vomer, small gape of mouth, toothless ectopterygoid and in the small number of branchiostegals, E. pussilus stands specialized alone among the catfishes. A diagnosis of the salient cranial characters of the fish is given and its relationship discussed.     

Solution Structure of an ABC Collagen Heterotrimer Reveals a Single-register Helix Stabilized by Electrostatic Interactions

Collagen, known for its structural role in tissues and also for its participation in the regulation of homeostatic and pathological processes in mammals, is assembled from triple helices that can be either homotrimers or heterotrimers. High resolution structural information for natural collagens has been difficult to obtain because of their size and the heterogeneity of their native environment. For this reason, peptides that self-assemble into collagen-like triple helices are used to gain insight into the structure, stability, and biochemistry of this important protein family. Although many of the most common collagens in humans are heterotrimers, almost all studies of collagen helices have been on homotrimers. Here we report the first structure of a collagen heterotrimer. Our structure, obtained by solution NMR, highlights the role of electrostatic interactions as stabilizing factors within the triple helical folding motif. This addresses an issue that has been actively researched because of the predominance of charged residues in the collagen family. We also find that it is possible to selectively form a collagen heterotrimer with a well defined composition and register of the peptide chains within the helix, based on information encoded solely in the collagenous domain. Globular domains are implicated in determining the composition of several collagen types, but it is unclear what their role in controlling register may be. We show that is possible to design peptides that not only selectively choose a composition but also a specific register without the assistance of other protein constructs. This mechanism may be used in nature as well.Collagens constitute an important structural protein family. They are found in the extracellular matrix and undergo a hierarchical self-assembly into large supramolecular structures with specific morphologies carefully crafted by nature to fulfill diverse structural and functional roles in a wide variety of tissues. In total, there are 28 known isoforms of collagen in humans arranged in a variety of structures and in a wide range of tissues. The feature defining this protein family is the presence of domains with uninterrupted Xaa-Yaa-Gly sequence repeats. These domains adopt a left-handed polyproline type II conformation because of the predominance of proline in the X position and hydroxyproline (Hyp = O), a post-translationally modified amino acid with a hydroxyl group on the γ-carbon of the proline side chain, in the Y position. Three such domains associate to form tightly packed right-handed triple helices in a folding motif commonly known as the collagen triple helix.Collagens are also implicated in pivotal homeostatic events in mammals such as the production of new vascular tissue and pathological conditions such as cancer metastasis (1). These processes are notoriously governed by interactions at the molecular level between cell surface proteins and the collagen triple helix and not by the morphology of the collagen aggregates (2, 3). Thus, an understanding of the collagen molecule and its interactions with other proteins at the atomic level has been actively pursued. However, because of its complex hierarchical self-assembly, and the scale of the resulting supramolecular structures, it is difficult to obtain information at atomic resolution for collagenous proteins (4). An approach developed to overcome this limitation is the use of short model peptides that adopt a triple helical fold (5). Such peptides have been used to study the structure (6, 7), folding (8), and dynamics (9) of the triple helix. These peptides have been shown to retain the biochemical properties of the higher assemblies found in their natural counterparts, binding to cell surface proteins such as integrins (10).Most of the studies performed on collagen mimetic peptides utilize triple helices with three identical chains called homotrimers (8, 11–13). Such systems are good models for some types of collagen, like type II. However, many of the most abundant types of collagen such as type I, IV, and IX are heterotrimeric species containing two (AAB) or three (ABC) different chains. Recently we introduced a new method to prepare heterotrimeric collagen like triple helices via noncovalent interactions (14–16). These systems have been primarily characterized through CD spectroscopy, which is a good indicator for the fold and stability of the peptides but lacks the ability to give detailed structural information. There are few studies available in the literature that utilize NMR to examine collagen heterotrimers; however, none of them use the technique to examine the structures of the assemblies in detail (17–20), and none result in a complete structural determination.A system of particular interest is composed of three peptides, (Pro-Lys-Gly)₁₀, (Asp-Hyp-Gly)₁₀, and (Pro-Hyp-Gly)₁₀, which we abbreviate K, D, and O respectively. Upon mixing and annealing of the peptides, CD studies indicate that an ABC triple helix with a surprisingly high thermal stability is formed (16). We hypothesized that the high thermal stability of these systems comes from the formation of charge pairs between lysine and aspartic acid. Homotrimeric model peptides that contain the sequence KGD, which occurs both in mammalian collagen (21) and bacterial collagen-like proteins (22), apparently also use this charge pairing. However, no structural information has been available to confirm the nature of the interactions.Here we study the K·D·O system using two- and three-dimensional NMR techniques to determine the composition and fold of the components of an annealed mixture of these three peptides. Also, for the first time, we are able to study the register or relative stagger of the peptide chains in the triple helix. In a collagen triple helix, the chains assemble staggered by one amino acid, so that there is always a glycine residue in every cross-section of the helix taken perpendicular to the helical axis. This allows the peptide chains to pack tightly while avoiding steric clashes in the center of the assembly. Depending on the nature of the leading, middle, and trailing chain, a total of six different assemblies, or registers, are possible for an ABC system (Fig. 1). Given the high thermal stability of the system, which allows for the recording of high quality NMR spectra, we found that our peptides preferentially populate one register, and using samples with strategically placed isotopically labeled amino acids, we are able to determine which one. Furthermore, we are able to obtain the first structure of a collagen triple helix in solution and give direct evidence of ionic hydrogen bonds as a stabilizing factor within the triple helical folding motif.Open in a separate windowFIGURE 1.Schematic N-terminal representation of the six possible registers for the heterotrimeric triple helix. The difference in the sequence is highlighted below each representation, where the position of glycine residues is marked by colored spheres.     

Eine neue Rubiaceen-Gattung aus der ägyptischen Flora

Ohne Zusammenfassung     

Platelet-rich plasma therapy - future or trend?

Chronic complex musculoskeletal injuries that are slow to heal pose challenges to physicians and researchers alike. Orthobiologics is a relatively newer science that involves application of naturally found materials from biological sources (for example, cell-based therapies), and offers exciting new possibilities to promote and accelerate bone and soft tissue healing. Platelet-rich plasma (PRP) is an orthobiologic that has recently gained popularity as an adjuvant treatment for musculoskeletal injuries. It is a volume of fractionated plasma from the patient''s own blood that contains platelet concentrate. The platelets contain alpha granules that are rich in several growth factors, such as platelet-derived growth factor, transforming growth factor-β, insulin-like growth factor, vascular endothelial growth factor and epidermal growth factor, which play key roles in tissue repair mechanisms. PRP has found application in diverse surgical fields to enhance bone and soft-tissue healing by placing supra-physiological concentrations of autologous platelets at the site of tissue damage. The relative ease of preparation, applicability in the clinical setting, favorable safety profile and possible beneficial outcome make PRP a promising therapeutic approach for future regenerative treatments. However, there is a large knowledge gap in our understanding of PRPs mechanism of action, which has raised skepticism regarding its potential efficacy and use. Thus, the aim of this review is to describe the various factors proposed to contribute to the biological activity of PRP, and the published pre-clinical and clinical evidence to support it. Additionally, we describe the current techniques and technology for PRP preparation, and review the present shortcomings of this therapy that will need to be overcome if it is to gain broad acceptance.     

Cyclophilin D regulates neuronal activity‐induced filopodiagenesis by fine‐tuning dendritic mitochondrial calcium dynamics

Recent studies have highlighted the role of mitochondria in dendritic protrusion growth and plasticity. However, the detailed mechanisms that mitochondria regulate dendritic filopodia morphogenesis remain elusive. Cyclophilin D (CypD, gene name: Ppif ) controls the opening of mitochondrial permeability transition pore. Although the pathological relevance of CypD has been intensively investigated, little is known about its physiological function in neurons. Here, we have found that genetic depletion of or pharmaceutical inhibition of CypD blunts the outgrowth of dendritic filopodia in response to KC l‐stimulated neuronal depolarization. Further cell biological studies suggest that such inhibitory effect of CypD loss‐of‐function is closely associated with compromised flexibility of dendritic mitochondrial calcium regulation during neuronal depolarization, as well as the resultant changes in intradendritic calcium homeostasis, calcium signaling activation, dendritic mitochondrial motility and redistribution. Interestingly, loss of CypD attenuates oxidative stress‐induced mitochondrial calcium perturbations and dendritic protrusion injury. Therefore, our study has revealed the physiological function of CypD in dendritic plasticity by acting as a fine‐tuner of mitochondrial calcium homeostasis. Moreover, CypD plays distinct roles in neuronal physiology and pathology.

Cover Image for this issue: doi: 10.1111/jnc.14189 .

     

Studies on the skull of the Indian sisorid catfish, Erethistes pussilus

The skull of Erethistes pussilus is described in detail. The general disposition of the bones corresponds to the siluroid pattern. Among the siluroid fishes, E. pussilus approaches the advanced forms in certain features such as obliteration of myodomic space, edentulous palate, absence of entopterygoids and supratemporals, intimate sutural articulation of posttemporals and complex vertebra with the cranium, diminished cranial cavity and loss of sutural articulation among the palatopterygoquadrate elements. In certain characters like the hyomandibula exclusively supported from the sphenotic, solitary hypohyal on each hyoid cornu, absence of interhyals, reduced orbits, edentulous vomer, small gape of mouth, toothless ectopterygoid and in the small number of branchiostegals, E. pussilus stands specialized alone among the catfishes. A diagnosis of the salient cranial characters of the fish is given and its relationship discussed.     

Eine ägyptischeCoris mit aktinomorphen Korollen

Ohne Zusammenfassung