Fear-avoidance model of chronic pain the next generation

Objective: The fear-avoidance (FA) model of chronic pain describes how individuals experiencing acute pain may become trapped into a vicious circle of chronic disability and suffering. We propose to extend the FA model by adopting a motivational perspective on chronic pain and disability. Methods: A narrative review. Results: There is ample evidence to support the validity of the FA model as originally formulated. There are, however, some key challenges that call for a next generation of the FA model. First, the FA model has its roots in psychopathology, and investigators will have to find a way to account for findings that do not easily fit within such framework. Second, the FA model needs to address the dynamics and complexities of disability and functional recovery. Third, the FA model should incorporate the idea that pain-related fear and avoidance occurs in a context of multiple and often competing personal goals. Discussion: To address these 3 key challenges, we argue that the next generation of the FA model needs to more explicitly adopt a motivational perspective, one that is built around the organizing powers of goals and self-regulatory processes. Using this framework, the FA model is recast as capturing the persistent but futile attempts to solve pain-related problems to protect and restore life goals

Mutational analysis of the carbohydrate binding activity of the tobacco lectin

At present the three-dimensional structure of the tobacco lectin, further referred to as Nictaba, and its carbohydrate-binding site are unresolved. In this paper, we propose a three-dimensional model for the Nictaba domain based on the homology between Nictaba and the carbohydrate-binding module 22 of Clostridium thermocellum Xyn10B. The suggested model nicely fits with results from circular dichroism experiments, indicating that Nictaba consists mainly of beta-sheet. In addition, the previously identified nuclear localization signal is located at the top of the protein as a part of a protruding loop. Judging from this model and sequence alignments with closely related proteins, conserved glutamic acid and tryptophan residues in the Nictaba sequence were selected for mutational analysis. The mutant DNA sequences as well as the original Nictaba sequence have been expressed in Pichia pastoris and the recombinant proteins were purified from the culture medium. Subsequently, the recombinant proteins were characterized and their carbohydrate binding properties analyzed with glycan array technology. It was shown that mutation of glutamic acid residues in the C-terminal half of the protein did not alter the carbohydrate-binding activity of the lectin. In contrast, mutation of tryptophan residues in the N-terminal half of the Nictaba domain resulted in a complete loss of carbohydrate binding activity. These results suggest that tryptophan residues play an important role in the carbohydrate binding site of Nictaba

Arabidopsis F-box protein containing a Nictaba-related lectin domain interacts with N-acetyllactosamine structures

The Arabidopsis thaliana genome contains a small group of bipartite F-box proteins, consisting of an N-terminal F-box domain and a C-terminal domain sharing sequence similarity with Nictaba, the jasmonate-induced glycan-binding protein (lectin) from tobacco. Based on the high sequence similarity between the C-terminal domain of these proteins and Nictaba, the hypothesis was put forward that the so-called F-box-Nictaba proteins possess carbohydrate-binding activity and accordingly can be considered functional homologs of the mammalian sugar-binding F-box or Fbs proteins which are involved in proteasomal degradation of glycoproteins. To obtain experimental evidence for the carbohydrate-binding activity and specificity of the A. thaliana F-box-Nictaba proteins, both the complete F-box-Nictaba sequence of one selected Arabidopsis F-box protein (in casu At2g02360) as well as the Nictaba-like domain only were expressed in Pichia pastoris and analyzed by affinity chromatography, agglutination assays and glycan micro-array binding assays. These results demonstrated that the C-terminal Nictaba-like domain provides the F-box-protein with a carbohydrate-binding activity that is specifically directed against N- and O-glycans containing N-acetyllactosamine (Galβ1-3GlcNAc and Galβ1-4GlcNAc) and poly-N-acetyllactosamine ([Galβ1-4GlcNAc](n)) as well as Lewis A (Galβ1-3(Fucα1-4)GlcNAc), Lewis X (Galβ1-4(Fucα1-3)GlcNAc, Lewis Y (Fucα1-2Galβ1-4(Fucα1-3)GlcNAc) and blood type B (Galα1-3(Fucα1-2)Galβ1-3GlcNAc) motifs. Based on these findings one can reasonably conclude that at least the A. thaliana F-box-Nictaba protein encoded by At2g02360 can act as a carbohydrate-binding protein. The results from the glycan array assays revealed differences in sugar-binding specificity between the F-box protein and Nictaba, indicating that the same carbohydrate-binding motif can accommodate unrelated oligosaccharides

Detection and Quantification of Citrullinated Chemokines

BACKGROUND: Posttranslational deimination or citrullination by peptidylarginine deiminases (PAD) regulates the biological function of proteins and may be involved in the development of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. This posttranslational modification of arginine was recently discovered on inflammatory chemokines including CXCL8 and CXCL10, and significantly reduced their biological activity. To evaluate the importance of these modified chemokines in patients, methods for the detection and quantification of citrullinated chemokines are needed. Since citrullination only results in an increase of the protein mass with one mass unit and the loss of one positive charge, selective biochemical detection is difficult. Therefore, we developed an antibody-based method to specifically detect and quantify citrullination on a protein of interest. METHODOLOGY/PRINCIPAL FINDINGS: First, the citrullinated proteins were chemically modified with antipyrine and 2,3-butanedione at low pH. Such selectively modified citrullines were subsequently detected and quantified by specific antibodies raised against a modified citrulline-containing peptide. The specificity of this two-step procedure was validated for citrullinated CXCL8 ([Cit(5)]CXCL8). Specific detection of [Cit(5)]CXCL8 concentrations between 1 and 50 ng/ml was possible, also in complex samples containing an excess of contaminating proteins. This novel detection method was used to evaluate the effect of lipopolysaccharide (LPS) on the citrullination of inflammatory chemokines induced in peripheral blood mononuclear cells (PBMCs) and granulocytes. LPS had no significant effect on the induction of CXCL8 citrullination in human PBMCs and granulocytes. However, granulocytes, known to contain PAD, were essential for the production of significant amounts of [Cit(5)]CXCL8. CONCLUSION/SIGNIFICANCE: The newly developed antibody-based method to specifically detect and quantify chemically modified citrullinated proteins is proven to be effective. This study furthermore demonstrates that granulocytes were essential to obtain significant levels of [Cit(5)]CXCL8. For human PBMCs and granulocytes stimulation with LPS did not affect the citrullination of CXCL8

The ‘diagonal’ approach to Global Fund financing: A cure for the broader malaise of health systems?

Background: The potentially destructive polarisation between 'vertical' financing (aiming for disease-specific results) and 'horizontal' financing (aiming for improved health systems) of health services in developing countries has found its way to the pages of Foreign Affairs and the Financial Times. The opportunity offered by 'diagonal' financing (aiming for disease-specific results through improved health systems) seems to be obscured in this polarisation. In April 2007, the board of the Global Fund to fight AIDS, Tuberculosis and Malaria agreed to consider comprehensive country health programmes for financing. The new International Health Partnership Plus, launched in September 2007, will help low-income countries to develop such programmes. The combination could lead the Global Fund to fight AIDS, Tuberculosis and Malaria to a much broader financing scope. Discussion: This evolution might be critical for the future of AIDS treatment in low-income countries, yet it is proposed at a time when the Global Fund to fight AIDS, Tuberculosis and Malaria is starved for resources. It might be unable to meet the needs of much broader and more expensive proposals. Furthermore, it might lose some of its exceptional features in the process: its aim for international sustainability, rather than in-country sustainability, and its capacity to circumvent spending restrictions imposed by the International Monetary Fund. Summary: The authors believe that a transformation of the Global Fund to fight AIDS, Tuberculosis and Malaria into a Global Health Fund is feasible, but only if accompanied by a substantial increase of donor commitments to the Global Fund. The transformation of the Global Fund into a 'diagonal' and ultimately perhaps 'horizontal' financing approach should happen gradually and carefully, and be accompanied by measures to safeguard its exceptional features

Los recursos hidrobiológicos en el río Iténez y sus tributarios: diversidad, aprovechamiento y manejo

La cuenca del río Iténez en Bolivia, o Guaporé en Brasil, se caracteriza por poseer una fauna acuática diversa, con características peculiares que la distinguen de las otras cuencas de la Amazonia boliviana. Este documento presenta una breve síntesis de la información disponible acerca de los recursos hidrobiológicos en esta cuenca y de las principales amenazas que están presentes dentro o fuera de la misma. Se da énfasis a los peces, reptiles y mamíferos. El caimán negro (Melanosuchus niger) y los mamíferos acuáticos (Pteronura brasiliensis e Inia boliviensis) se encuentran vulnerables o en peligro según el último Libro Rojo de la fauna silvestre de Bolivia, y las estrategias para garantizar su conservación están en proceso de construcción. Por otro lado, la cuenca alberga un conjunto de peces de elevada diversidad y con una composición típica para sistemas de aguas claras. En las partes bajas de la cuenca, los peces forman parte esencial de la dieta de los pobladores amazónicos y en algunos lugares están sujetos a un aprovechamiento comercial en el marco de legislación local específica. Algo similar ocurre con el lagarto (Caiman yacare), aprovechado en el marco de un programa nacional creado para beneficiar a pueblos indígenas. Estos recursos ayudan a sostener los medios de vida de los pobladores locales y a obtener ingresos económicos a nivel familiar y regional. Basados en estas informaciones, se concluye que urgen estrategias para conservar los servicios ambientales de la cuenca Iténez.A bacia Iténez na Bolivia, ou Guaporé, no Brasil, é caracterizada por ter urna fauna aquática diversificada, com características únicas que a distinguem das outras bacías da Amazonia boliviana. Este artigo apresenta um breve resumo da informado disponível sobre os recursos aquáticos da bacia e as principais ameaças que estão presentes dentro ou tora da bacia. Ojacaré-açu (Melanosuchus niger) e mamíferos aquáticos (lontra Pteronura brasiliensis e golfinho Inia boliviensis) sao vulneráveis ou ameaçadas de extinção de acordo com o mais recente Livro Vermelho, e as estratégias para garantir a sua preservado estao em construido. Por outro lado, a sub-bacia albergue um conjunto de peixes de alta diversidade, com urna composição típica para sistemas de água clara. Nas partes mais baixas da bacia, os peixes sao urna parte essencial da dieta das comunidades da Amazonia e em alguns lugares estao sujeitos a exploração comercial que ocorre dentro do quadro regulamentar de legislção específica. Algo semelhante acontece com o jacaré (Caiman yacare), aproveitado no contexto de um programa específico criado para beneficiar os povos indígenas. Estes recursos ajudam a sustentar os meios de subsistencia da população local e obter renda nos níveis familiar e regional. Com base nessas informagoes, conclui-se que as estratégias sao urgentes para conservar e gerir os serviços ambientais na bacía Iténez.The Iténez River basin in Bolivia, or Guapore in Brazil, is characterized by its diverse aquatic fauna, with some unique traits differentiating it from the other river basins of the Bolivian Amazon. This article presents a brief synthesis of the available information about the hydrobiological resources in the Iténez basin and about the main threats present within and outside the basin. Emphasis is put on reptiles, fish and mammals. The black caiman (Melanosuchus niger) and the aquatic mammals (giant otter Pteronura brasiliensis and river dolphin Inia boliviensis) are vulnerable or in danger of extinction according to the latest Red Book, and strategies for their conservation are being designed. On the other hand, the basin hosts a highly diverse fish community, and with a composition typical for ‘clear’ or low turbidity river systems. In the lower parts of the basin, several of the fish species are part of the diet of the Amazon human communities, and in some places are subject to commercial fishing which occurs within a specific legal framework. A similar situation occurs with the caiman (Caiman yacare), which is exploited within the framework of a national program created to provide benefit to indigenous communities. These resources help to sustain the means of subsistence of the local population by contributing income at the family and regional levels. Based on these informations, we conclude that strategies are urgently needed to conserve and manage the environmental Services delivered by the aquatic systems of this basin