Conceptualization and measurement of integrated human service networks for evaluation

Introduction: Integration has been advanced as a strategy for the delivery of a number of human services that have traditionally been delivered by autonomous agencies with independent processes and funding sources. However, measurement of the dimensions of integration has been hampered by numerous factors, including a lack of definitional and conceptual clarity of integration, and the use of measurement tools with atheoretical foundations and limited psychometric testing. Theoryymethods: Based on a review of integration measurement approaches, a comprehensive approach to the measure of multiple dimensions of integrated human service networks was conceptualized. The combination of concepts was derived from existing theoretical, policy, and measurement approaches in order to establish the content validity and comprehensiveness of the proposed measure. Results: The dimensions of human service integration measures are: (1) Observed (current) and expected structural inputs, or the mix of agencies that comprise the network (e.g. extent, scope, depth, congruence within an agency, and reciprocity between agencies). (2) Functioning of the network both in terms of the quality of the network or partnership functioning and ingredients of the integration of the networks’ working arrangements and range of human services provided. (3) Network outputs in terms of network capacity (e.g. what is accomplished, for how many and how quickly given the local demand) measured from dual perspectives of the agency and the family. Conclusion: This newly developed measure unites multiple perspectives in a comprehensive approach to the measurement of integration of human service networks. Content validity has been established. Future work should focus on further refinement of this instrument through psychometric evaluation (e.g. construct validity) in diverse networks and relating these measures of network integration to client and system outcomes

Deciphering the Arginine-Binding Preferences at the Substrate-Binding Groove of Ser/Thr Kinases by Computational Surface Mapping

Protein kinases are key signaling enzymes that catalyze the transfer of γ-phosphate from an ATP molecule to a phospho-accepting residue in the substrate. Unraveling the molecular features that govern the preference of kinases for particular residues flanking the phosphoacceptor is important for understanding kinase specificities toward their substrates and for designing substrate-like peptidic inhibitors. We applied ANCHORSmap, a new fragment-based computational approach for mapping amino acid side chains on protein surfaces, to predict and characterize the preference of kinases toward Arginine binding. We focus on positions P−2 and P−5, commonly occupied by Arginine (Arg) in substrates of basophilic Ser/Thr kinases. The method accurately identified all the P−2/P−5 Arg binding sites previously determined by X-ray crystallography and produced Arg preferences that corresponded to those experimentally found by peptide arrays. The predicted Arg-binding positions and their associated pockets were analyzed in terms of shape, physicochemical properties, amino acid composition, and in-silico mutagenesis, providing structural rationalization for previously unexplained trends in kinase preferences toward Arg moieties. This methodology sheds light on several kinases that were described in the literature as having non-trivial preferences for Arg, and provides some surprising departures from the prevailing views regarding residues that determine kinase specificity toward Arg. In particular, we found that the preference for a P−5 Arg is not necessarily governed by the 170/230 acidic pair, as was previously assumed, but by several different pairs of acidic residues, selected from positions 133, 169, and 230 (PKA numbering). The acidic residue at position 230 serves as a pivotal element in recognizing Arg from both the P−2 and P−5 positions

Mechanism of wound healing in annelids

All animals possess some type of tissue repair mechanism. In some species, the capacity to repair tissues is limited to the healing of wounds, but others posses a striking repair capability to replace the entire organs. It has been reported that some mechanisms, namely extracellular matrix remodeling, appear to occur in most repair processes. However, it remains unclear to what extent the process of wound healing is similar to organ regeneration

Nucleosides and glutamine are primary energy substrates for embryonic and adult chicken red cells

It has been assumed that glucose is a major energy yielding substrate for chicken red blood cells. In this report we show that glucose fails to maintain cellular ATP levels in embryonic and mature chicken erythrocytes during overnight incubation. Of over a dozen metabolites tested, inosine, guanosine, and glutamine were the most efficacious ATP-sustaining substrates. Of seven potential citric acid cycle substrates, only glutamine significantly sustained ATP levels. Incubation with inosine plus glutamine sustained the ATP level at over 70% of the initial value found in embryonic chicken red cells. Uridine, cytidine, xanthosine, glutamate, and pyruvate were ineffective substrates. Similar results were obtained with adult erythrocytes, except that glutamine plus inosine fully sustained ATP levels during long-term incubation. Adenosine did not sustain ATP levels. Below 1 mM, the adenosine level was rapidly exhausted and above 1 mM its presence led to cell lysis. The ability of some nucleosides to maintain ATP levels is consistent with the high numbers of nitrobenzylthioinosine binding sites (nucleoside transporter sites) both in mature chicken red cells (~ 10 000 sites/cell) and in embryonic red cells (~ 30 000 sites/cell). Unlike pig red cells which switch from glucose to nucleosides at the erythrocyte stage, chicken cells show primary dependence on nucleoside metabolism at the embryonic stage.Key words: red cells, glucose transport, nucleoside transport, glutamine transport, cellular ATP. </jats:p

Loss of glucose transporters is an early event in differentiation of HD3 cells

The HD3 cell, a chicken erythroblast cell line infected with a temperature-sensitive avian erythroblastosis virus, becomes committed to differentiate to an erythrocyte upon temperature shift in presence of inducers. Before induction, the HD3 cell transports glucose and 2-deoxyglucose (2-DG). 3-O-methylglucose is poorly taken up. Upon induction of differentiation, glucose and 2-DG transport activity fall. Twenty-four hours postinduction, up to 75% of the glucose transport activity may disappear. By use of cDNA probes for chicken glucose transporters, two species of mRNA of 3.1 and 1.7 kb (equivalent to mammalian GLUT1 and GLUT3 mRNA, respectively) are detected. Both messages virtually disappear within 48 h after induction. Run-on assays show the cessation of synthesis of the corresponding RNAs parallel to the loss of glucose transport. In contrast to the glucose transporters, the nucleoside transporter level increases after induction of hematopoiesis. This developmental pattern is consistent with earlier studies showing that mature chicken erythrocytes have little glucose transport activity but retain appreciable levels of the nucleoside transporter and that nucleosides and glutamine provide major sources of oxidizable carbon compounds to sustain metabolism in circulating chicken erythrocytes.</jats:p