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Selected AbstractsThe chemotaxis defect of Shwachman-Diamond Syndrome leukocytesCYTOSKELETON, Issue 3 2004Vesna Stepanovic Abstract Shwachman-Diamond Syndrome (SDS) is a rare autosomal recessive, multisystem disorder presenting in childhood with intermittent neutropenia and pancreatic insufficiency. It is characterized by recurrent infections independent of neutropenia, suggesting a functional neutrophil defect. While mutations at a single gene locus (SBDS) appear to be responsible for SDS in a majority of patients, the function of that gene and a specific defect in SDS neutrophil behavior have not been elucidated. Therefore, employing 2D and 3D computer-assisted motion analysis systems, we have analyzed the basic motile behavior and chemotactic responsiveness of individual polymorphonuclear leukocytes (PMNs) of 14 clinically diagnosed SDS patients. It is demonstrated that the basic motile behavior of SDS PMNs is normal in the absence of chemoattractant, that SDS PMNs respond normally to increasing and decreasing temporal gradients of the chemoattractant fMLP, and that SDS PMNs exhibit a normal chemokinetic response to a spatial gradient of fMLP. fMLP receptors were also distributed uniformly through the plasma membrane of SDS PMNs as in control PMNs. SDS PMNs, however, were incapable of orienting in and chemotaxing up a spatial gradient of fMLP. This unique defect in orientation was manifested by the PMNs of every SDS patient tested. The PMNs of an SDS patient who had received an allogenic hematopoietic stem cell transplant, as well as PMNs from a cystic fibrosis patient, oriented normally. These results suggest that the defect in SDS PMNs is in a specific pathway emanating from the fMLP receptor that is involved exclusively in regulating orientation in response to a spatial gradient of fMLP. This pathway must function in parallel with additional pathways, intact in SDS patients, that emanate from the fMLP receptor and regulate responses to temporal rather than spatial changes in receptor occupancy. Cell Motil. Cytoskeleton 57:158,174, 2004. © 2004 Wiley-Liss, Inc. [source] Self-expandable metallic stents for palliation of malignant esophageal obstruction: special reference to quality of life and survival of patientsDISEASES OF THE ESOPHAGUS, Issue 1 2004K. Yajima SUMMARY., Self-expandable metallic stents (EMS) provide a common option for malignant esophageal stenosis because of the low complication rate and high dysphagia improvement rate. However, there are few studies on the functional duration of EMS and the extent of improvement of the quality of life. We retrospectively analyzed 18 patients who received EMSs in our division from 1996 to 2002. The median duration of possible food intake and the median survival period were 94.5 and 108 days. The median duration of domiciliary treatment was 56 days. Six of the 18 patients were not discharged from hospital after EMS insertion. The Karnofsky index was found to be a significant determinant of the feasibility of domiciliary treatment. One-third of the patients are incapable of obtaining the benefits of the palliative therapy. EMS deployment should be prudently selected for patients exhibiting low performance status. [source] What neurobiology cannot tell us about addictionADDICTION, Issue 5 2010Harold Kalant ABSTRACT Molecular neurobiological studies have yielded enormous amounts of valuable information about neuronal response mechanisms and their adaptive changes. However, in relation to addiction this information is of limited value because almost every cell function appears to be involved. Thus it tells us only that neurons adapt to ,addictive drugs' as they do to all sorts of other functional disturbances. This information may be of limited help in the development of potential auxiliary agents for treatment of addiction. However, a reductionist approach which attempts to analyse addiction at ever finer levels of structure and function, is inherently incapable of explaining what causes these mechanisms to be brought into play in some cases and not in others, or by self-administration of a drug but not by passive exposure. There is abundant evidence that psychological, social, economic and specific situational factors play important roles in initiating addiction, in addition to genetic and other biological factors. Therefore, if we hope to be able to make predictions at any but a statistical level, or to develop effective means of prevention, it is necessary to devise appropriate integrative approaches to the study of addiction, rather than pursue an ever-finer reductive approach which leads steadily farther away from the complex interaction of drug, user, environment and specific situations that characterizes the problem in humans. [source] Kleptoplasty in an Antarctic dinoflagellate: caught in evolutionary transition?ENVIRONMENTAL MICROBIOLOGY, Issue 1 2007Rebecca J. Gast Summary Photosynthetic dinoflagellates contain a diverse collection of plastid types, a situation believed to have arisen from multiple endosymbiotic events. In addition, a number of heterotrophic (phagotrophic) dinoflagellates possess the ability to acquire chloroplasts temporarily by engulfing algae and retaining their chloroplasts in a functional state. These latter relationships typically last from a few days to weeks, at which point the chloroplasts lose function, are digested and replaced with newly acquired plastids. A novel and abundant dinoflagellate related to the icthyotoxic genera Karenia and Karlodinium was recently discovered by us in the Ross Sea, Antarctica. Sequencing of its plastid small subunit ribosomal gene indicated that it did not share evolutionary history with the plastids of Karenia or Karlodinium, but was closely related to the free-living haptophyte Phaeocystis antarctica, a species that often dominates phytoplankton blooms in the Ross Sea. Chloroplast uptake was observed to occur rapidly (within 2 days), with retention in cultures being long-lived (several months) but not permanent. The dinoflagellate was also incapable of growing indefinitely in continuous darkness with algae as prey. Our findings may indicate an emerging endosymbiotic event yielding a dinoflagellate that is presently neither purely phototrophic nor purely heterotrophic, but occupies a niche juxtaposed between these contrasting nutritional modes. [source] Proliferation and interleukin,5 production by CD8hiCD57+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2008Abstract CD8hiCD57+ T cells have previously been described as effector memory T cells with minimal expansion capacity and high susceptibility to activation-induced cell death. In contrast, we demonstrate here that CD8hiCD57+ T cells are capable of rapid expansion using multiple techniques including [3H]thymidine uptake, flow cytometric bead-based enumeration and standard haemocytometer counting. Previous reports can be explained by marked inhibition of activation-induced expansion and increased 7-amino-actinomycin,D uptake by CD8hiCD57+ T cells following treatment with CFSE, a dye previously used to measure their proliferation, combined with specific media requirements for the growth of this cell subset. The ability of CD8hiCD57+ T cells to further differentiate is highlighted by a distinct cytokine profile late after activation that includes the unexpected release of high levels of interleukin,5. These data indicate that CD8hiCD57+ T cells should not be considered as "end-stage" effector T cells incapable of proliferation, but represent a highly differentiated subset capable of rapid division and exhibiting novel functions separate from their previously described cytotoxic and IFN-, responses. [source] Quality of life in 1000 patients with early relapsing,remitting multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2009N. Putzki Background and purpose:, To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing,remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNß-1a) treatment. Methods:, Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNß-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). Results:, A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58,1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51,0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75,0.78) vs. 0.75 (95%CI: 0.74,0.76) at baseline, 95%CI for difference: 0.01,0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. Conclusions:, Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNß attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems. [source] Olfactory bulb hypoplasia in Prokr2 null mice stems from defective neuronal progenitor migration and differentiationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Haydn M. Prosser Abstract New neurons are added on a daily basis to the olfactory bulb (OB) of a mammal, and this phenomenon exists throughout its lifetime. These new cells are born in the subventricular zone and migrate to the OB via the rostral migratory stream (RMS). To examine the role of the prokineticin receptor 2 (Prokr2) in neurogenesis, we created a Prokr2 null mouse, and report a decrease in the volume of its OB and also a decrease in the number of bromodeoxyuridine (BrdU)-positive cells. There is disrupted architecture of the OB, with the glomerular layer containing terminal dUTP nick-end labeling (TUNEL) -positive nuclei and also a decrease in tyrosine hydroxylase-positive neurons in this layer. In addition, there are increased numbers of doublecortin-positive neuroblasts in the RMS and increased PSA-NCAM (polysialylated form of the neural cell adhesion molecule) -positive neuronal progenitors around the olfactory ventricle, indicating their detachment from homotypic chains is compromised. Finally, in support of this, Prokr2-deficient cells expanded in vitro as neurospheres are incapable of migrating towards a source of recombinant human prokineticin 2 (PROK2). Together, these findings suggest an important role for Prokr2 in OB neurogenesis. [source] Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Tali Kobilo Abstract The brain endocannabinoid system has been shown to play a role in memory, though the extent to which this role generalizes over different types and processes of memory is not yet determined. Here we show that the cannabinoid receptor 1 (CB1) plays differential roles in acquisition, extinction and reconsolidation of conditioned taste aversion (CTA) memory in the rat insular cortex, which contains the taste cortex. Activation of the CB1 receptor in the insular cortex inhibits acquisition and reconsolidation but not extinction, whereas blockade of the CB1 receptor promotes memory and blocks extinction of CTA, while having no apparent effect on reconsolidation. The CB1 ligands used in this study were incapable of substituting the unconditioned stimulus in CTA training. All in all, the data raise the possibility that the state of activity of the CB1 receptor in the insular cortex contributes to the encoding of hedonic valence that enters into association with taste items. [source] EMPIRICAL COMPARISON OF G MATRIX TEST STATISTICS: FINDING BIOLOGICALLY RELEVANT CHANGEEVOLUTION, Issue 10 2009Brittny Calsbeek A central assumption of quantitative genetic theory is that the breeder's equation (R=GP,1S) accurately predicts the evolutionary response to selection. Recent studies highlight the fact that the additive genetic variance,covariance matrix (G) may change over time, rendering the breeder's equation incapable of predicting evolutionary change over more than a few generations. Although some consensus on whether G changes over time has been reached, multiple, often-incompatible methods for comparing G matrices are currently used. A major challenge of G matrix comparison is determining the biological relevance of observed change. Here, we develop a "selection skewers"G matrix comparison statistic that uses the breeder's equation to compare the response to selection given two G matrices while holding selection intensity constant. We present a bootstrap algorithm that determines the significance of G matrix differences using the selection skewers method, random skewers, Mantel's and Bartlett's tests, and eigenanalysis. We then compare these methods by applying the bootstrap to a dataset of laboratory populations of Tribolium castaneum. We find that the results of matrix comparison statistics are inconsistent based on differing a priori goals of each test, and that the selection skewers method is useful for identifying biologically relevant G matrix differences. [source] Increased bacterial load in shrimp hemolymph in the absence of prophenoloxidaseFEBS JOURNAL, Issue 18 2009Fernand F. Fagutao Invertebrates rely on their innate immune responses to protect themselves from pathogens, one of which is melanization of bacteria mediated by the activation of phenoloxidase (PO). Furthermore, invertebrate hemolymph, even that of healthy individuals, has been shown to contain bacterial species. The mechanisms that prevent these bacteria from proliferating and becoming deleterious to the host are, however, poorly understood. Here, we show that knocking down the activity of the inactive precursor of PO [prophenoloxidase (proPO)] by RNA interference resulted in a significant increase in the bacterial load of kuruma shrimp, Marsupenaeus japonicus, even in the absence of a bacterial or viral challenge. Silencing of proPO also led to a sharp increase in shrimp mortality. In addition, the hemolymph of proPO-depleted shrimp had significantly lower hemocyte counts and PO activity than control samples. Microarray analysis after proPO silencing also showed a decrease in the expression of a few antimicrobial peptides, but no effect on the expression of the genes involved in the clotting system. Treatment with antibiotics prior to and after proPO dsRNA injection, to counteract the loss of proPO, resulted in a significant increase in shrimp survival. Our results therefore show that the absence of proPO renders the shrimp incapable of controlling bacteria present in the hemolymph, and that proPO is therefore essential for its survival. [source] Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitroFEBS JOURNAL, Issue 17 2009Suzana Kovac Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin,gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin,ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8,10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo. Structured digital abstract ,,MINT-7212832, MINT-7212849: Apo-transferrin (uniprotkb:P02787) and Gamide (uniprotkb:P01350) bind (MI:0407) by surface plasmon resonance (MI:0107) ,,MINT-7212881, MINT-7212909: Ggly (uniprotkb:P01350) and Apo-transferrin (uniprotkb:P02787) bind (MI:0407) by cross-linking studies (MI:0030) ,,MINT-7212864: Apo-transferrin (uniprotkb:P02787) and Ggly (uniprotkb:P01350) bind (MI:0407) by competition binding (MI:0405) [source] Cooperation of two carotene desaturases in the production of lycopene in Myxococcus xanthusFEBS JOURNAL, Issue 16 2007Antonio A. Iniesta In Myxococcus xanthus, all known carotenogenic genes are grouped together in the gene cluster carB,carA, except for one, crtIb (previously named carC). We show here that the first three genes of the carB operon, crtE, crtIa, and crtB, encode a geranygeranyl synthase, a phytoene desaturase, and a phytoene synthase, respectively. We demonstrate also that CrtIa possesses cis -to- trans isomerase activity, and is able to dehydrogenate phytoene, producing phytofluene and ,-carotene. Unlike the majority of CrtI-type phytoene desaturases, CrtIa is unable to perform the four dehydrogenation events involved in converting phytoene to lycopene. CrtIb, on the other hand, is incapable of dehydrogenating phytoene and lacks cis -to- trans isomerase activity. However, the presence of both CrtIa and CrtIb allows the completion of the four desaturation steps that convert phytoene to lycopene. Therefore, we report a unique mechanism where two distinct CrtI-type desaturases cooperate to carry out the four desaturation steps required for lycopene formation. In addition, we show that there is a difference in substrate recognition between the two desaturases; CrtIa dehydrogenates carotenes in the cis conformation, whereas CrtIb dehydrogenates carotenes in the trans conformation. [source] Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cellsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Joseph M. Bliss Abstract This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans -specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell,cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections. [source] The phosphorylated C-terminal domain of Xenopus Cut5 directly mediates ATR-dependent activation of Chk1GENES TO CELLS, Issue 9 2006Yoshitami Hashimoto ATR-dependent activation of the kinase Chk1 is the initial step in signal transduction in the DNA replication checkpoint, which allows a cell to enter mitosis only after the completion of DNA replication. TopBP1-related proteins in higher eukaryotes are implicated in the replication checkpoint, but their exact role remains elusive because of their requirements for replication initiation. Here we report that the initiation function of Xenopus Cut5/TopBP1 could be entirely separated from its checkpoint function: the N-terminal half fragment, a region of Cut5 conserved through evolution, is sufficient for initiation, but is incapable of activating the checkpoint; the C-terminal half fragment, which is unique in metazoan species, is by itself capable of activating the checkpoint response without initiating replication. Upon the activation of Chk1, the Ser1131 within the C-terminal region of Cut5 is phosphorylated, and this phosphorylation is critical for the checkpoint response. Furthermore, Cut5 directly stimulated Chk1 phosphorylation in the in vitro kinase assay reconstituted with recombinant proteins and ATR immunoprecipitated from extracts. On the basis of replication protein A (RPA)-dependent loading of Cut5 on to replicating and replication-arrested chromatin, we propose that Cut5 plays a crucial role in the initial amplification step of the ATR-Chk1 signaling pathway at the stalled replication fork. [source] The Space of Local Control in the Devolution of us Public Housing PolicyGEOGRAFISKA ANNALER SERIES B: HUMAN GEOGRAPHY, Issue 4 2000Janet L. Smith Sweeping changes in national policy aim to radically transform public housing in the United States. The goal is to reduce social isolation and increase opportunities for low income tenants by demolishing ,worst case' housing, most of which is modern, high-rise buildings with high vacancy and crime rates, and replacing it with ,mixed-income' developments and tenant based assistance to disperse current public housing families. Transformation relies on the national government devolving more decision-making power to local government and public housing authorities. The assumption here is that decentralizing the responsibility for public housing will yield more effective results and be more efficient. This paper explores the problematic nature of decentralization as it has been conceptualized in policy discourse, focusing on the underlying assumptions about the benefits of increasing local control in the implementation of national policy. As this paper describes, this conceived space of local control does not take into account the spatial features that have historically shaped where and how low income families live in the US, including racism and classism and a general aversion by the market to produce affordable rental units and mixed-income developments. As a result, this conceived space of local control places the burden on low income residents to make transformation a success. To make this case, Wittgenstein's (1958) post-structural view of language is combined with Lefebvre's view of space to provide a framework in which to examine US housing policy discourse as a ,space producing' activity. The Chicago Housing Authority's Plan for Transformation is used to illustrate how local efforts to transform public housing reproduce a functional space for local control that is incapable of generating many of the proposed benefits of decentralization for public housing tenants. [source] Expression of 5-lipoxygenase (5-LOX) in T lymphocytesIMMUNOLOGY, Issue 2 2007Jeanne M. Cook-Moreau Summary 5-lipoxygenase (5-LOX) is the key enzyme responsible for the synthesis of the biologically active leukotrienes. Its presence has been reported in cells of the myeloid lineage and B lymphocytes but has not been formally defined in T lymphocytes. In this study, we provide evidence for 5-LOX expression on both transcriptional and translational levels in highly purified peripheral blood T cells as well as in human T lymphoblastoid cell lines (MOLT4 and Jurkat). Messenger RNA (mRNA) of 5-LOX was amplified by conventional reverse transcription,polymerase chain reaction (RT-PCR; MOLT4 and Jurkat cells) and by in situ RT-PCR (T lymphocytes). 5-LOX protein expression was confirmed by Western blot and immunofluorescence studies. 5-LOX was present primarily in the cytoplasm with some nuclear localization and was translocated to the nuclear periphery after culture in a mitosis-supporting medium. Fluorescence-activated cell sorter analysis of different T-lymphocyte populations, including CD4, CD8, CD45RO, CD45RA, T helper type 2, and T-cell receptor-,, and -,, expressing cells, did not identify a differential distribution of the enzyme. Purified peripheral blood T lymphocytes were incapable of synthesizing leukotrienes in the absence of exogenous arachidonic acid. Jurkat cells produced leukotriene C4 and a small amount of leukotriene B4 in response to CD3,CD28 cross-linking. This synthesis was abolished by two inhibitors of leukotriene synthesis, MK-886 and AA-861. The presence of 5-LOX in T lymphocytes but the absence of endogenous lipoxygenase metabolite production compared to Jurkat cells may constitute a fundamental difference between resting peripheral lymphocytes and leukaemic cells. [source] Interferon-, activation of polymorphonuclear neutrophil functionIMMUNOLOGY, Issue 1 2004Terri N. Ellis Summary As current research illuminates the dynamic interplay between the innate and acquired immune responses, the interaction and communication between these two arms has yet to be fully investigated. Polymorphonuclear neutrophils (PMNs) and interferon-, (IFN-,) are known critical components of innate and acquired immunity, respectively. However, recent studies have demonstrated that these two components are not entirely isolated. Treatment of PMNs with IFN-, elicits a variety of responses depending on stimuli and environmental conditions. These responses include increased oxidative burst, differential gene expression, and induction of antigen presentation. Many of these functions have been overlooked in PMNs, which have long been classified as terminal phagocytic cells incapable of protein synthesis. As this review reports, the old definition of the PMN is in need of an update, as these cells have demonstrated their ability to mediate the transition between the innate and acquired immune responses. [source] Disc structure function and its potential for repairINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2002J. Melrose The intervertebral disc (IVD) is the largest predominantly avascular, aneural, alymphatic structure of the human body. It provides articulation between adjoining vertebral bodies and also acts as a weight-bearing cushion dissipating axially applied spinal loads. The IVD is composed of an outer collagen-rich annulus fibrosus (AF) and a central proteoglycan (PG)-rich nucleus pulposus (NP). Superior and inferior cartilaginous endplates (CEPs), thin layers of hyaline-like cartilage, cover the ends of the vertebral bodies. The AF is composed of concentric layers (lamellae) which contain variable proportions of type I and II collagen, this tissue has high tensile strength. The NP in contrast is a gelatinous PG-rich tissue which provides weight-bearing properties to the composite disc structure. With the onset of age, cells in the NP progressively die as this tissue becomes depleted of PGs, less hydrated and more fibrous as the disc undergoes an age-dependent fibrocartilaginous transformation. Such age-dependent cellular and matrix changes can decrease the discs' biomechanical competence and trauma can further lead to failure of structural components of the disc. Annular defects are fairly common and include vertebral rim-lesions, concentric (circumferential) annular tears (separation of adjacent annular lamellae) and radial annular tears (clefts which initiate within the NP). While vascular in-growth around annular tears has been noted, evidence from human post-mortem studies indicate they have a limited ability to undergo repair. Several experimental approaches are currently under evaluation for their ability to promote the repair of such annular lesions. These include growth of AF fibrochondrocytes on a resorbable polycaprolactone (PCL) bio-membrane.1 Sheets of fibrochondrocytes lay down type-I collagen and actin stress fibres on PCL. These matrix components are important for the spatial assembly of the collagenous lamella during annular development and correct phenotypic expression of cells in biomatrices.1 An alternative approach employs preparation of tissue engineered IVDs where AF and NP cells are separately cultured in polyglycolic acid and sodium alginate biomatrices, either separately or within a manifold designed to reproduce the required IVD dimensions for its use as a prospective implant device.2 AF and NP cells have also been grown on tissue culture inserts after their recovery from alginate bead culture to form plugs of tissue engineered cartilage.3 A key component in this latter strategy was the stimulation of the high density disc cell cultures with osteogenic protein-1 (OP-1) 200 ng/mL.3 This resulted in the production of tissue engineered AF and NP plugs with compositions, histochemical characteristics and biomechanical properties approaching those of the native disc tissues.2,3 Such materials hold reat promise in future applications as disc or annular implants. The introduction of appropriate genes into disc cells by gene transduction methodology using adenoviral vectors or ,gene-gun' delivery systems also holds considerable promise for the promotion of disc repair processes.4 Such an approach with the OP-1 gene is particularly appealing.5 The anchoring of discal implants to vertebral bodies has also been evaluated by several approaches. A 3D fabric based polyethylene biocomposite holds much promise as one such anchorage device6 while biological glues used to seal fibrocartilaginous structures such as the AF and meniscus8 following surgical intervention, also hold promise in this area. Several very promising new experimental approaches and strategies are therefore currently under evaluation for the improvement of discal repair. The aforementioned IVD defects are a common cause of disc failure and sites of increased nerve in-growth in symptomatic IVDs in man and are thus often sources of sciatic-type pain. Annular defects such as those described above have formerly been considered incapable of undergoing spontaneous repair thus a clear need exists for interventions which might improve on their repair. Based on the rapid rate of progress and the examples outlined above one may optimistically suggest that a successful remedy to this troublesome clinical entity will be developed in the not so distant future. References 1JohnsonWEBet al. (2001) Directed cytoskeletal orientation and intervertebral disc cell growth: towards the development of annular repair techniques. Trans Orthop Res Soc26, 894. 2MizunoHet al. (2001) Tissue engineering of a composite intervertebral disc. Trans Orthop Res Soc26, 78. 3MatsumotoTet al. (2001) Formation of transplantable disc shaped tissues by nucleus pulposus and annulus fibrosus cells: biochemical and biomechanical properties. Trans Orthop Res Soc26, 897. 4NishidaKet al. (2000) Potential applications of gene therapy to the treatment of intervertebral disc disorders. Clin Orthop Rel Res379 (Suppl), S234,S241. 5MatsumotoTet al. (2001) Transfer of osteogenic protein-1 gene by gene gun system promotes matrix synthesis in bovine intervertebral disc and articular cartilage cells. Trans Orthop Res Soc26, 30. 6ShikinamiY , Kawarada (1998) Potential application of a triaxial three-dimensional fabric (3-DF) as an implant. Biomaterials19, 617,35. [source] Tentative evaluation of the impact of public transfers on the dynamics of poverty: The case of RussiaINTERNATIONAL SOCIAL SECURITY REVIEW, Issue 1 2007Matthieu Clément The aim of this article is to offer a dynamic impact analysis of the system of transfers in Russia, based on a comparison of indicators of well-being measured before and after state intervention. We shall begin by assessing the impact of public transfers on different forms of poverty and demonstrate that, while the system is seeing a fall in chronic and transitional poverty, there is very little movement between categories. We shall then evaluate the capacity of the system to keep non-poor households from falling into poverty (protection) and to help poor households escape poverty (promotion). Several studies suggest that the Russian system of transfers is well suited to protection but has proved incapable of attaining the goal of promotion. In other words, in its current form it cannot claim to be an effective tool to combat long-term poverty. [source] The Globalization of Taxation?INTERNATIONAL STUDIES QUARTERLY, Issue 2 2003Electronic Commerce, the Transformation of the State The anticipated growth of new communications technologies, including the Internet and other digital networks, will make it increasingly difficult for states to tax global commerce effectively. Greater harmonization and coordination of national tax policies will likely be required in the coming years in order to address this problem. Given that the history of the state is inseparable from the history of taxation, this "globalization of taxation" could have far-reaching political implications. The modern state itself emerged out of a fiscal crisis of medieval European feudalism, which by the 14th and 15th centuries was increasingly incapable of raising sufficient revenues to support the mounting expenses of warfare. If new developments in the technology of commerce are now undermining the efficiency of the state as an autonomous taxing entity, fiscal pressures may produce a similar shift in de facto political authority away from the state and toward whatever international mechanisms are created to expedite the taxation of these new forms of commerce. [source] Generalized Diffusion Tensor Imaging (GDTI): A Method for Characterizing and Imaging Diffusion Anisotropy Caused by Non-Gaussian DiffusionISRAEL JOURNAL OF CHEMISTRY, Issue 1-2 2003Chunlei Liu For non-Gaussian distributed random displacement, which is common in restricted diffusion, a second-order diffusion tensor is incapable of fully characterizing the diffusion process. The insufficiency of a second-order tensor is evident in the limited capability of diffusion tensor imaging (DTI) in resolving multiple fiber orientations within one voxel of human white matter. A generalized diffusion tensor imaging (GDTI) method was recently proposed to solve this problem by generalizing Fick's law to a higher-order partial differential equation (PDE). The relationship between the higher-order tensor coefficients of the PDE and the higher-order cumulants of the random displacement can be derived. The statistical property of the diffusion process was fully characterized via the higher-order tensor coefficients by reconstructing the probability density function (PDF) of the molecular random displacement. Those higher-order tensor coefficients can be measured using conventional diffusion-weighted imaging or spectroscopy techniques. Simulations demonstrated that this method was capable of quantitatively characterizing non-Gaussian diffusion and accurately resolving multiple fiber orientations. It can be shown that this method is consistent with the q-space approach. The second-order approximation of GDTI was shown to be DTI. [source] Protease-Activated Receptors: A Means of Converting Extracellular Proteolysis into Intracellular SignalsIUBMB LIFE, Issue 6 2002E. J. Mackie Abstract Protease-activated receptors (PARs) mediate cellular responses to a variety of extracellular proteases. The four known PARs constitute a subgroup of the family of seven-transmembrane domain G protein-coupled receptors and activate intracellular signalling pathways typical for this family of receptors. Activation of PARs involves proteolytic cleavage of the extracellular domain, resulting in formation of a new N terminus, which acts as a tethered ligand. PAR-1, -3, and -4 are relatively selective for activation by thrombin whereas PAR-2 is activated by a variety of proteases, including trypsin and tryptase. Recent studies in mice genetically incapable of expressing specific PARs have defined roles for PAR-1 in vascular development, and for PAR-3 and -4 in platelet activation, which plays a fundamental role in blood coagulation. PAR-1 has also been implicated in a variety of other biological processes including inflammation, and brain and muscle development. Responses mediated by PAR-2 include contraction of intestinal smooth muscle, epithelium-dependent smooth muscle relaxation in the airways and vasculature, and potentiation of inflammatory responses. The area of PAR research is rapidly expanding our understanding of how cells communicate and control biological functions, in turn increasing our knowledge of disease processes and providing potential targets for therapeutic intervention. [source] Pain assessment in older people with dementia: literature reviewJOURNAL OF ADVANCED NURSING, Issue 1 2009Linda McAuliffe Abstract Title.,Pain assessment in older people with dementia: literature review. Aim., This paper is a report of a literature review conducted to identify barriers to successful pain assessment in older adults with dementia and possible strategies to overcome such barriers. Background., Pain is frequently undetected, misinterpreted, or inaccurately assessed in older adults with cognitive impairment. These people are often unable to articulate or convey how they feel and are often perceived as incapable of experiencing or recalling pain. Data sources., Searches were conducted of CINAHL, Medline and other databases for the period 1993,2007 using the search terms pain, dementia, assess*, barrier* and obstacle*. Methods., Studies were critically appraised by two independent reviewers. Data were extracted using instruments specifically developed for the review. Studies were categorized according to levels of evidence defined by the Australian National Health and Medical Research Council and Joanna Briggs Institute. Results., Perceived barriers to successful pain assessment in people with dementia included lack of recognition of pain, lack of sufficient education and/or training, misdiagnosis or late diagnosis, and non-use of assessment tools. Barriers related to people with dementia included insufficient evidence, the possibility of a ,no pain' subset of people with dementia, type of pain, and stoical attitudes. Strategies proposed as means of overcoming these barriers included knowing the person, knowing by diversity/intuitive perception, education and training, and use of adequate tools. Conclusion., More extensive education and training about the relationship between pain and dementia are urgently needed, as is the development and implementation of an effective pain assessment tool specifically designed to detect and measure pain in older adults with all stages of dementia. [source] Hybrid Bayesian networks: making the hybrid Bayesian classifier robust to missing training dataJOURNAL OF CHEMOMETRICS, Issue 5 2003Nathaniel A. Woody Abstract Many standard classification methods are incapable of handling missing values in a sample. Instead, these methods must rely on external filling methods in order to estimate the missing values. The hybrid network proposed in this paper is an extension of the hybrid classifier that is robust to missing values. The hybrid network is produced by performing empirical Bayesian network structure learning to create a Bayesian network that retains its classification ability in the presence of missing data in both training and test cases. The performance of the hybrid network is measured by calculating a misclassification rate when data are removed from a dataset. These misclassification curves are then compared against similar curves produced from the hybrid classifier and from a classification tree. Copyright © 2003 John Wiley & Sons, Ltd. [source] The SARS Crisis: Was Anybody Responsible?JOURNAL OF CONTINGENCIES AND CRISIS MANAGEMENT, Issue 2 2006Stephanie Buus As scholars in fields such as media studies, crisis studies and public policy studies have argued, there exists a fundamental link between crises and the media. Once an event has been interpreted as a crisis, questions of accountability inevitably appear on the media agenda, and the struggle to attribute blame and responsibility to a specific entity or entities,the blame game,thus becomes an inexorable part of the crisis process. Focusing on three liberal Western newspapers with an international, primarily Western elite readership and a reputation for in-depth analysis of global events, The Economist, the Financial Times and the International Herald Tribune, this article employs Iyengar's and Valkenburg's notions of responsibility frames to examine whether initial coverage of the 2003 SARS crisis in these accounts held any particular entity accountable for the crisis, looks at three key themes used to communicate to the reader a particular way of thinking about responsibility for SARS and examines some of the consequences of the kind of responsibility frame constructed around the SARS crisis in these accounts. As our findings show, there is an entity that the early news accounts studied consistently held responsible for the 2003 SARS crisis, the Chinese system, and the corresponding responsibility frame at operation in these accounts is thematic rather than episodic in nature, since it consistently places the SARS crisis within a broader context (a product of "China" itself and/or of societal-governmental forces in China) rather than in relation to a specific episode or as the result of the particular actions of individuals. The SARS crisis narrative therefore presented in these accounts tells the story of an anachronistic Chinese system faced with a contemporary health threat that, by its very nature, it is incapable of assessing accurately or managing responsibly. By way of conclusion, we argue that, while the use of such a thematic frame to explain China's role in the 2003 SARS crisis may be accurate in certain respects, this frame falls short in other respects and proves particularly inadequate to the challenge of capturing the economic complexities of China's role during the crisis. [source] Validation of the AMPF,STR® MiniFilerTM PCR Amplification Kit for Use in Forensic Casework,JOURNAL OF FORENSIC SCIENCES, Issue 5 2009Coral Luce M.S. Abstract:, The AmpF,STR® MiniFilerTM PCR Amplification Kit is designed to genotype degraded and/or inhibited DNA samples when the AmpF,STR® IdentifilerTM PCR Amplification Kit is incapable of generating a complete genetic profile. Validation experiments, following the SWGDAM guidelines, were designed to evaluate the performance of MiniFiler. Data obtained demonstrated that MiniFiler, when used in conjunction with Identifiler, provided an increased ability to obtain genetic profiles from challenged samples. The optimum template range was found to be between 0.2 and 0.6 ng, with 0.3 ng yielding the best results. Full concordance was achieved between the MiniFiler kit and Identifiler kit except in a single case of a null allele at locus D21S11. Numerous instances of severe heterozygous peak imbalance (<50%) were observed in single source samples amplified within the optimum range of input DNA suggesting that caution be taken when attempting to deduce component genotypes in a mixture. [source] Expanding radiation quarantine treatments beyond fruit fliesAGRICULTURAL AND FOREST ENTOMOLOGY, Issue 2 2000Guy J. Hallman Abstract 1 The potential of ionizing radiation as a disinfestation treatment for insects other than tephritid fruit flies is discussed. Radiation quarantine treatments are unique in that insects are not killed immediately but rendered sterile or incapable of completing development. 2 The most tolerant insect stage to radiation is that which is most developed. Female insects, but not always mites, are sterilized with equal or lower doses than males. 3 Insects irradiated with sterilizing doses usually have shorter longevities than non-irradiated ones. Low oxygen conditions often increase tolerance to radiation. 4 Insects in diapause are not more tolerant of radiation than non-diapausing ones. 5 Some pests of several groups, such as aphids, whiteflies, weevils, scarab beetles, and fruit flies, may be controlled with doses ,,100 Gy. Some lepidopterous pests and most mites require about 300 Gy. Stored product moths may require as much as 1 kGy to sterilize, and nematodes could need >,4 kGy. 6 Even though application of irradiation to pallet-loads of produce could mean that up to three times the minimum required dose is applied to the perimeter of the pallet, many fresh commodities tolerate doses required for quarantine security against many quarantined pests. Irradiation is arguably the most widely applicable quarantine treatment from the standpoint of commodity quality. [source] Prosecuting ,Gross' Medical Negligence: Manslaughter, Discretion, and the Crown Prosecution ServiceJOURNAL OF LAW AND SOCIETY, Issue 3 2006Oliver Quick This article examines prosecutions of health care professionals for gross negligence manslaughter following fatal errors committed in the course of their work. Unease has long surrounded the use of ,gross negligence' as a form of criminal liability, and particularly as it applies to health care professions operating in high-risk settings. The recent dramatic rise of such prosecutions calls for a closer understanding of the processes by which important prosecutorial decisions are made. In particular, this calls for an investigation into the exercise of discretion by prosecutors in interpreting the loosely defined and contested concept of gross negligence. This article analyses data obtained from a statistical analysis of ,medical manslaughter' cases and also from interviews with crown prosecutors. Discussion of the main findings leads to the conclusion that the offence of gross negligence manslaughter is incapable of any objective and fair measurement and ought to be abolished. [source] EXCHANGES OF INFORMATION, ENERGY & MATERIALS IN SYMBIOSESJOURNAL OF PHYCOLOGY, Issue 2000J.A. Raven Symbiosis is important in the cell and environmental biology of algae. Some examples involving the author and numerous collaborators include: 1) chloroplasts of eukaryotic algae arose from endosymbioses. Plastids are incapable of independent existence; most of the genes of the cyanobacterial photobiont have been lost, and the majority of the rest have been transferred to the nuclear genome. Some of the genes retained by the plastid are those whose transcription is controlled by environmental cues transduced by the organelle. The general trend is for organelle genes to be transferred to the nucleus, escaping plastid redox activities generating mutagenic free radicals; 2) symbioses involving potentially free-living photobionts include marine lichens and sponges with cyanobacterial symbionts. For the lichen, Lichina, inorganic carbon acquisition appears to involve inorganic carbon transport by the mycobiont, and for the sponge, Cymbastella, the flagellar activity of the sponge is probably important for inorganic carbon supply to the photobiont; 3) the Australasian fucalean, Notheia, is an obligate epiphyte on the fucaleans, Hormosira and Xiphophora; the four species involved all contain the hexitol, altritol. Notheia anomala is known to be phyletically-distant from the other five altritol-containing species. Can Notheia synthesize altritol, or is it obtained from the phorophyte?; 4) Sacoglossan gastropods retain kleptoplastids (not strictly symbionts) from ulvophycean (or rhodophycean) marine algae. Analyses of the natural abundance of stable carbon isotopes suggest significant contribution of kleptoplastid photosynthesis to the carbon and energy budget of the mollusks. [source] Ultrastructure of Lobocharacium coloradoense, gen. et sp. nov. (Chlorophyta, Characiosiphonaceae), an unusual coenocyte from ColoradoJOURNAL OF PHYCOLOGY, Issue 2 2000Paul Kugrens Light and electron microscopic descriptions are provided for Lobocharacium coloradoense, gen. et sp. nov., a unicellular coenocytic green alga isolated from a power plant's retaining pond in north-central Colorado. Vegetative cells range from 120,230 ,m in length and 80,120 ,m in diameter in culture. The large vegetative cells are attached to substrates by small discoid attachment pads. The cells are multinucleate and consist of distinct cytoplasmic lobes, with each lobe containing a chloroplast and a basal nucleus. Chloroplasts are somewhat cone-shaped in profile and stellate or lobed when viewed from the surface, and each has a central, basal pyrenoid. Hundreds of these cytoplasmic lobes occur within a cell, and thin cytoplasmic bridges interconnect the lobes. When a vegetative cell matures, each of the cytoplasmic lobes cleaves to form numerous fusiform zoospores or spherical isogametes. The biflagellate isogametes range in size from 4,10 ,m, they lack a cell wall, they have a cup-shaped chloroplast with a pyrenoid and stigma, and they have a nucleus close to the basal bodies. Isogametes are incapable of forming vegetative cells. Zoospores are biflagellate and fusiform, measuring 8,12 ,m in length and 4,6 ,m in diameter. Each zoospore has a cell wall, a single parietal chloroplast with a prominent pyrenoid in the center of the chloroplast, and a long oval stigma. Gamete and zoospore release involves a dissolution of the entire vegetative wall. Released zoospores usually settle and cluster near the vegetative cell from which they were produced, attach to the substrate with their flagella, and, shortly after losing their flagella, extrude mucilage through the flagellar pores in the wall to form a small discoid attachment pad. The incipient vegetative cell is fusiform and uninucleate, but it becomes more rounded and multinucleate as enlargement occurs. Most vegetative cells in culture become dormant, and the chloroplast becomes orange in color. Some cells form single aplanospores that can withstand desiccation, but occasionally numerous aplanospores may also be formed later in the larger vegetative cells. [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||