Mechanisms of hematopoietic stem cell mobilization: When innate immunity assails the cells that make blood and bone

Mobilization is now used worldwide to collect large numbers of hematopoietic stem and progenitor cells (HSPCs) for transplantation. Although the first mobilizing agents were discovered largely by accident, discovery of more efficient mobilizing agents will require a better understanding of the molecular mechanisms responsible. During the past 5 years, a number of mechanisms have been identified, shedding new light on the dynamics of the hematopoietic system in vivo and on the intricate relationship between hematopoiesis, innate immunity, and bone. After briefly reviewing the mechanisms by which circulating HSPCs home into the bone marrow and what keeps them there, the current knowledge of mechanisms responsible for HSPC mobilization in response to hematopoietic growth factors such as granulocyte colony-stimulating factor, chemotherapy, chemokines, and polyanions will be discussed together with current strategies developed to further increase HSPC mobilization. (c) 2006 International Society for Experimental Hematology.

C-reactive protein mediates CD11b expression in monocytes through the non-receptor tyrosine kinase, Syk, and calcium mobilization but not through cytosolic peroxides

Objective: C-Reactive protein (CRP) can modulate integrin surface expression on monocytes following Fcγ receptor engagement. We have investigated the signal transduction events causing this phenotypic alteration. Methods: CRP-induced signalling events were examined in THP-1 and primary monocytes, measuring Syk phosphorylation by Western blotting, intracellular Ca2+ ([Ca2+]i) by Indo-1 fluorescence and surface expression of CD11b by flow cytometry. Cytosolic peroxides were determined by DCF fluorescence. Results: CRP induced phosphorylation of Syk and an increase in [Ca2+]i both of which were inhibitable by the Syk specific antagonist, piceatannol. Piceatannol also inhibited the CRP-induced increase in surface CD11b. In addition, pre-treatment of primary monoytes with the Ca2+ mobiliser, thapsigargin, increased CD11b expression; this effect was accentuated in the presence of CRP but was abolished in the presence of the [Ca2+]i chelator, BAPTA. CRP also increased cytosolic peroxide levels; this effect was attenuated by antioxidants (ascorbate, α-tocopherol), expression of surface CD11b not being inhibited by antioxidants alone. Conclusion: CRP induces CD11b expression in monocytes through a peroxide independent pathway involving both Syk phosphorylation and [Ca2+]i release. © Birkhäuser Verlag, 2005.

Reform of the New Zealand Health System:problematization, mobilization and change

This paper will seek to explicate the changes in the New Zealand health sector informed by the concepts of problematization, inscription and the construction of networks (Callon, 1986; Latour, 1987, 1993). This will involve applying a framework of interpretation based on the concepts of Latour's sociology of translation. Material on problematization and inscription will be incorporated into the paper in order to provide an explanatory frame of reference which will enable us to make sense of the processes of change in the New Zealand health sector. The sociology of translation will be used to explain the processes which underlie the changes and will be used to capture effects, such as changes in policy and structure, producing new networks within which 'allies' could be enrolled in support of the health reforms.

Studies of the cationic polymerisation of vinylic and energetic cyclic ether monomers

The cationic polymerisation of various monomers, including cyclic ethers bearing energetic nitrate ester (-ON02) groups, substituted styrenes and isobutylene has been investigated. The main reaction studied has been the ring-opening polymerisation of 3- (nitratomethyl)-3-methyl oxetane (NIMMO) using the alcohol/BF3.0Et2 binary initiator system. A series of di-, tri- and tetrafunctional telechelic polymers has been synthesised. In order to optimise the system, achieve controlled molecular weight polymers and understand the mechanism of polymerisation the effects of certain parameters on the molecular weight distribution, as determined by Size Exclusion Chromatography, have been examined. This shows the molecular weight achieved depends on a combination of factors including -OH concentration, addition rate of monomer and, most importantly, temperature. A lower temperature and OH concentration tends to produce higher molecular weight, whereas, slower addition rates of monomer, either have no significant effect or produce a lower molecular weight polymer. These factors were used to increase the formation of a cyclic oligomer, by a side reaction, and suggest, that the polymerisation of NIMMO is complicated with endbiting and back biting reactions, along with other transfer/termination processes. These observations appear to fit the model of an active-chain end mechanism. Another cyclic monomer, glycidyl nitrate (GLYN), has been polymerised by the activated monomer mechanism. Various other monomers have been used to end-cap the polymer chains to produce hydroxy ends which are expected to form more stable urethane links, than the glycidyl nitrate ends, when cured with isocyanates. A novel monomer, butadiene oxide dinitrate (BODN), has been prepared and its homopolymerisation and copolymerisation with GL YN studied. In concurrent work the carbocationic polymerisations of isobutylene or substituted styrenes have been studied. Materials with narrow molecular weight distributions have been prepared using the diphenyl phosphate/BCl3 initiator. These systems and monomers are expected to be used in the synthesis of thermoplastic elastomers.

Nitric oxide-dependent bone marrow progenitor mobilization by carbon monoxide enhances endothelial repair after vascular injury

Carbon monoxide (CO) has emerged as a vascular homeostatic molecule that prevents balloon angioplasty-induced stenosis via antiproliferative effects on vascular smooth muscle cells. The effects of CO on reendothelialization have not been evaluated.

Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity

Background - MHC Class I molecules present antigenic peptides to cytotoxic T cells, which forms an integral part of the adaptive immune response. Peptides are bound within a groove formed by the MHC heavy chain. Previous approaches to MHC Class I-peptide binding prediction have largely concentrated on the peptide anchor residues located at the P2 and C-terminus positions. Results - A large dataset comprising MHC-peptide structural complexes was created by re-modelling pre-determined x-ray crystallographic structures. Static energetic analysis, following energy minimisation, was performed on the dataset in order to characterise interactions between bound peptides and the MHC Class I molecule, partitioning the interactions within the groove into van der Waals, electrostatic and total non-bonded energy contributions. Conclusion - The QSAR techniques of Genetic Function Approximation (GFA) and Genetic Partial Least Squares (G/PLS) algorithms were used to identify key interactions between the two molecules by comparing the calculated energy values with experimentally-determined BL50 data. Although the peptide termini binding interactions help ensure the stability of the MHC Class I-peptide complex, the central region of the peptide is also important in defining the specificity of the interaction. As thermodynamic studies indicate that peptide association and dissociation may be driven entropically, it may be necessary to incorporate entropic contributions into future calculations.

Systematic financial resources allocation processes:a model for critical resources mobilization and deployment for nigerian universities

Purpose – The purpose of this research is to study the perceived impact of some factors on the resources allocation processes of the Nigerian universities and to suggest a framework that will help practitioners and academics to understand and improve such processes. Design/methodology/approach – The study adopted the interpretive qualitative approach aimed at an ‘in-depth’ understanding of the resource allocation experiences of key university personnel and their perceived impact of the contextual factors affecting such processes. The analysis of individual narratives from each university established the conditions and factors impacting the resources allocation processes within each institution. Findings – The resources allocation process issues in the Nigerian universities may be categorised into people (core and peripheral units’ challenge, and politics and power); process (resources allocation processes); and resources (critical financial shortage and resources dependence response). The study also provides insight that resourcing efficiency in Nigerian universities appears strongly constrained by the rivalry among the resource managers. The efficient resources allocation process (ERAP) model is proposed to resolve the identified resourcing deficiencies. Research limitations/implications – The research is not focused to provide generalizable observations but ‘in-depth’ perceived factors and their impact on the resources allocation processes in Nigerian universities. The study is limited to the internal resources allocation issues within the universities and excludes the external funding factors. The resource managers’ responses to the identified factors may affect their internal resourcing efficiency. Further research using more empirical samples is required to obtain more widespread results and the implications for all universities. Originality/value – This study contributes a fresh literature framework to resources allocation processes focusing at ‘people’, ‘process’ and ‘resources’. Also a middle range theory triangulation is developed in relation to better understanding of resourcing process management. The study will be of interest to university managers and policy makers.

On arterial contractility, energetic requirements of the cardiovascular system, and the formation of arterial sclerosis

The aorta has been viewed as a passive distribution manifold for blood whose elasticity allows it to store blood during cardiac ejection (systole), and release it during relaxation (diastole). This capacitance, or compliance, lowers peak cardiac work input and maintains peripheral sanguine irrigation throughout the cardiac cycle. The compliance of the human and canine circulatory systems have been described either as constant throughout the cycle (Toy et al. 1985) or as some inverse function of pressure (Li et al. 1990, Cappelo et al. 1995). This work shows that a compliance value that is higher during systole than diastole (equivalent to a direct function of pressure) leads to a reduction in the energetic input to the cardiovascular system (CV), even when accounting for the energy required to change compliance. This conclusion is obtained numerically, based on a 3-element lumped-parameter model of the CV, then demonstrated in a physical model built for the purpose. It is then shown, based on the numerical and physical models, on analytical considerations of elastic tubes, and on the analysis of arterial volume as a function of pressure measured in vivo (Armentano et al. 1995), that the mechanical effects of a presupposed arterial contraction are consistent with those of energetically beneficial changes in compliance during the cardiac cycle. Although the amount of energy potentially saved with rhythmically contracting arteries is small (mean 0.55% for the cases studied) the importance of the phenomenon lies in its possible relation to another function of the arterial smooth muscle (ASM): synthesis of wall matrix macromolecules. It is speculated that a reduction in the rate of collagen synthesis by the ASM is implicated in the formation of arteriosclerosis. ^

Mobilization of Pollutant-Degrading Bacteria by Eukaryotic Zoospores

Peer reviewed

Without an empire: Muslim mobilization after the caliphate

The Caliphate was a fundamental part of Islamic society for nearly 1300 years. This paper seeks to uncover what effect the removal of this institution had on the mobilization of Muslims in several parts of the world; Turkey, Egypt, and British India. These countries had unique experiences with colonialism, secularism, nationalism, that in many ways conditioned the response of individuals to this momentous occasion. Each country’s reaction had a profound impact on the future trajectory of civil society, and the role of Islam in the lives of its citizens. The conclusions of this paper challenge the monolithic depiction of Islam in the world, and reveal the origins of conflict that these three centers of Muslim power face today. Much of the religious narrative now commonplace in Muslim organizations derive from this pivotal event in world history.