Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice

Exacerbated sensitivity to mechanical stimuli that are normally innocuous or mildly painful (mechanical allodynia and hyperalgesia) occurs during inflammation and underlies painful diseases. Proteases that are generated during inflammation and disease cleave protease-activated receptor 2 (PAR2) on afferent nerves to cause mechanical hyperalgesia in the skin and intestine by unknown mechanisms. We hypothesized that PAR2-mediated mechanical hyperalgesia requires sensitization of the ion channel transient receptor potential vanilloid 4 (TRPV4). Immunoreactive TRPV4 was coexpressed by rat dorsal root ganglia (DRG) neurons with PAR2, substance P (SP) and calcitonin gene-related peptide (CGRP), mediators of pain transmission. In PAR2-expressing cell lines that either naturally expressed TRPV4 (bronchial epithelial cells) or that were transfected to express TRPV4 (HEK cells), pretreatment with a PAR2 agonist enhanced Ca2+ and current responses to the TRPV4 agonists phorbol ester 4alpha-phorbol 12,13-didecanoate (4alphaPDD) and hypotonic solutions. PAR2-agonist similarly sensitized TRPV4 Ca2+ signals and currents in DRG neurons. Antagonists of phospholipase Cbeta and protein kinases A, C and D inhibited PAR2-induced sensitization of TRPV4 Ca2+ signals and currents. 4alphaPDD and hypotonic solutions stimulated SP and CGRP release from dorsal horn of rat spinal cord, and pretreatment with PAR2 agonist sensitized TRPV4-dependent peptide release. Intraplantar injection of PAR2 agonist caused mechanical hyperalgesia in mice and sensitized pain responses to the TRPV4 agonists 4alphaPDD and hypotonic solutions. Deletion of TRPV4 prevented PAR2 agonist-induced mechanical hyperalgesia and sensitization. This novel mechanism, by which PAR2 activates a second messenger to sensitize TRPV4-dependent release of nociceptive peptides and induce mechanical hyperalgesia, may underlie inflammatory hyperalgesia in diseases where proteases are activated and released.

Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia

Inflammatory proteases (mast cell tryptase and trypsins) cleave protease-activated receptor 2 (PAR2) on spinal afferent neurons and cause persistent inflammation and hyperalgesia by unknown mechanisms. We determined whether transient receptor potential vanilloid receptor 1 (TRPV1), a cation channel activated by capsaicin, protons, and noxious heat, mediates PAR2-induced hyperalgesia. PAR2 was coexpressed with TRPV1 in small- to medium-diameter neurons of the dorsal root ganglia (DRG), as determined by immunofluorescence. PAR2 agonists increased intracellular [Ca2+] ([Ca2+]i) in these neurons in culture, and PAR2-responsive neurons also responded to the TRPV1 agonist capsaicin, confirming coexpression of PAR2 and TRPV1. PAR2 agonists potentiated capsaicin-induced increases in [Ca2+]i in TRPV1-transfected human embryonic kidney (HEK) cells and DRG neurons and potentiated capsaicin-induced currents in DRG neurons. Inhibitors of phospholipase C and protein kinase C (PKC) suppressed PAR2-induced sensitization of TRPV1-mediated changes in [Ca2+]i and TRPV1 currents. Activation of PAR2 or PKC induced phosphorylation of TRPV1 in HEK cells, suggesting a direct regulation of the channel. Intraplantar injection of a PAR2 agonist caused persistent thermal hyperalgesia that was prevented by antagonism or deletion of TRPV1. Coinjection of nonhyperalgesic doses of PAR2 agonist and capsaicin induced hyperalgesia that was inhibited by deletion of TRPV1 or antagonism of PKC. PAR2 activation also potentiated capsaicin-induced release of substance P and calcitonin gene-related peptide from superfused segments of the dorsal horn of the spinal cord, where they mediate hyperalgesia. We have identified a novel mechanism by which proteases that activate PAR2 sensitize TRPV1 through PKC. Antagonism of PAR2, TRPV1, or PKC may abrogate protease-induced thermal hyperalgesia.

Holocene and Pleistocene pluvial periods in Yemen, Southern Arabia

Arabia is an important potential pathway for the dispersal of Homo sapiens (“out of Africa”). Yet, because of its arid to hyper-arid climate humans could only migrate across southern Arabia during pluvial periods when environmental conditions were favorable. However, knowledge on the timing of Arabian pluvial periods prior to the Holocene is mainly based on a single and possibly incomplete speleothem record from Hoti Cave in Northern Oman. Additional terrestrial records from the Arabian Peninsula are needed to confirm the Hoti Cave record. Here we present a new speleothem record from Mukalla Cave in southern Yemen. The Mukalla Cave and Hoti Cave records clearly reveal that speleothems growth occurred solely during peak interglacial periods, corresponding to Marine Isotope Stages (MIS) 1 (early to mid-Holocene), 5.1, 5.3, 5.5 (Eemian), 7.1, 7.5 and 9. Of these humid periods, highest precipitation occurred during MIS 5.5 and lowest during early to middle Holocene.

Sharing power? Prospects for a U.S. concert-balance strategy

The Pax Americana and the grand strategy of hegemony (or “Primacy”) that underpins it may be becoming unsustainable. Particularly in the wake of exhausting wars, the Global Financial Crisis, and the shift of wealth from West to East, it may no longer be possible or prudent for the United States to act as the unipolar sheriff or guardian of a world order. But how viable are the alternatives, and what difficulties will these alternatives entail in their design and execution? This analysis offers a sympathetic but critical analysis of alternative U.S. National Security Strategies of “retrenchment” that critics of American diplomacy offer. In these strategies, the United States would anticipate the coming of a more multipolar world and organize its behavior around the dual principles of “concert” and “balance,” seeking a collaborative relationship with other great powers, while being prepared to counterbalance any hostile aggressor that threatens world order. The proponents of such strategies argue that by scaling back its global military presence and its commitments, the United States can trade prestige for security, shift burdens, and attain a more free hand. To support this theory, they often look to the 19th-century concert of Europe as a model of a successful security regime and to general theories about the natural balancing behavior of states. This monograph examines this precedent and measures its usefulness for contemporary statecraft to identify how great power concerts are sustained and how they break down. The project also applies competing theories to how states might behave if world politics are in transition: Will they balance, bandwagon, or hedge? This demonstrates the multiple possible futures that could shape and be shaped by a new strategy. viii A new strategy based on an acceptance of multipolarity and the limits of power is prudent. There is scope for such a shift. The convergence of several trends—including transnational problems needing collaborative efforts, the military advantages of defenders, the reluctance of states to engage in unbridled competition, and hegemony fatigue among the American people—means that an opportunity exists internationally and at home for a shift to a new strategy. But a Concert-Balance strategy will still need to deal with several potential dilemmas. These include the difficulty of reconciling competitive balancing with cooperative concerts, the limits of balancing without a forward-reaching onshore military capability, possible unanticipated consequences such as a rise in regional power competition or the emergence of blocs (such as a Chinese East Asia or an Iranian Gulf), and the challenge of sustaining domestic political support for a strategy that voluntarily abdicates world leadership. These difficulties can be mitigated, but they must be met with pragmatic and gradual implementation as well as elegant theorizing and the need to avoid swapping one ironclad, doctrinaire grand strategy for another.

International terrorism, domestic political instability, and the escalation effect

What are the main causes of international terrorism? Despite the meticulous examination of various candidate explanations, existing estimates still diverge in sign, size, and significance. This article puts forward a novel explanation and supporting evidence. We argue that domestic political instability provides the learning environment needed to successfully execute international terror attacks. Using a yearly panel of 123 countries over 1973–2003, we find that the occurrence of civil wars increases fatalities and the number of international terrorist acts by 45%. These results hold for alternative indicators of political instability, estimators, subsamples, subperiods, and accounting for competing explanations.

Outward bound: women translators and scientific travel writing, 1780–1800

As the Enlightenment drew to a close, translation had gradually acquired an increasingly important role in the international circulation and transmission of scientific knowledge. Yet comparatively little attention has been paid to the translators responsible for making such accounts accessible in other languages, some of whom were women. In this article I explore how European women cast themselves as intellectually enquiring, knowledgeable and authoritative figures in their translations. Focusing specifically on the genre of scientific travel writing, I investigate the narrative strategies deployed by women translators to mark their involvement in the process of scientific knowledge-making. These strategies ranged from rhetorical near-invisibility, driven by women's modest marginalization of their own public engagement in science, to the active advertisement of themselves as intellectually curious consumers of scientific knowledge. A detailed study of Elizabeth Helme's translation of the French ornithologist Françoise le Vaillant's Voyage dans l'intérieur de l'Afrique [Voyage into the Interior of Africa] (1790) allows me to explore how her reworking of the original text for an Anglophone reading public enabled her to engage cautiously – or sometimes more openly – with questions regarding how scientific knowledge was constructed, for whom and with which aims in mind.

Species diversity and dominance-richness relationships for ground and arboreal ant (Hymenoptera: Formicidae) assemblages in Namibian desert, saltpan, and savannah

Namibia has high levels of invertebrate endemism, but biodiversity research has been geographically and taxonomically limited. In South African savannah, species richness of ground-foraging ant assemblages is regulated by dominant ant species, but this pattern has not been tested in other arid environments. In this study, we provide a description of ant diversity at baits in three different Namibian habitats (savannah, saltpan and desert), and we test the relationship between ant dominance and richness for ground-foraging and arboreal species. Forty-two ant species were collected in this study, with species richness being highest in the saltpan, followed by savannah and then desert. Ant assemblages were most similar between the savannah and desert, due to shared arboreal species. Similarity between savannah and saltpan ant assemblages was due to an overlap in ground-foraging species. Ground ants were more diverse than arboreal ants, and several species were observed at baits for both strata, although the degree of overlap varied with habitat type. The dominance-richness relationship varied depending on habitat and sampling strata. We found a unimodal relationship in the saltpan, but not in the savannah. For ground ants the relationship was logarithmic, with increasing abundance of dominants leading to decreasing overall species richness. However, no trend was observed for the arboreal ant assemblage. In the desert, low ant abundance meant that we were unable to assign species dominance, possibly due to reduced foraging activity caused by high temperatures. The lack of a consistent dominance-richness trend across assemblages may be the result of varying degrees of environmental stress or competition. Our study is a preliminary description of diversity and dominance in Namibia, and we hope it stimulates further research on ant assemblages in arid regions of Africa.

O descompasso de uma experiência: avaliação do Programa Habitar Brasil na Comunidade África-Natal/RN

This research deals with the evaluation of the Programa do Governo Federal para Urbanização de Favelas Habitar Brasil(1993) carried out in the Africa slum - Redinha neighbourhood in Natal-Rn. This study carried out in period from 2005 to 2006 searches to identify the effects of the actions proposed by Program in 1993-1994 about the current urbanistic configuration of the Africa community. It analyzes the effectiveness in the process of achievement of the considered objectives to habitation, communitity equipments, infrastructure and agrarian regularization. On the evaluation process, it has been as reference the works developed by Adauto Cardoso (2004), Blaine Worthen (2004), Ronaldo Garcia (2001) and Rosângela Paz (2006). About the Habitational Policy with approach to the Urbanistic Right and the right to the housing, the reflections by Raquel Rolnik, Nabil Bonduki, Ermínia Maricato, Saule Júnior, Betânia de Moraes Alfonsin and Edésio Fernandes are main references. To gauge the execution of the objectives proposed by Habitar Brasil in 1993, it has searched in the documentary data of the time and in information gotten in interviews with technicians that had participated of the program, consistent references on what was considered, what was executed and the process of the intervention of Habitar Brasil in the Africa community. The area analysis in 2005-2006 has developed on the base of the urbanistic survey of the current situation from the four performance lines of the Program: habitation, infrastructure, community equipments and agrarian regularization, with a current urbanistic evaluation of Africa considering the intervention carried out in 1993 and 1994. The study points out the context of Brazilian Habitational Policy where the Programa Habitar Brasil was launched, explaining the main principles of the Program. In terms of local, it empahsizes the administrative-political factors that had contributed so that Natal-Rn city has been pioneering in the resources captation of Habitar Brazil (1993). Considering Habitar Brazil in Africa, the work argues and presents the intervention diagnosis and the proposal, developed by Program in 1993 evidencing the local problem of the time. After that, it makes a current reading of the area, identifying in 2006 representative elements of Habitar Brasil (1993-1994) for the Africa community. It identifies significant advances in the constitution of the institucional apparatus of the plaining system of Habitation of Social Interest for the city of Natal and points the fragilities in the implementation of the urban infrastructure actions and above all in the achievement of the objectives of the agrarian regularization

Phylogenetic relationships within the speciose family Characidae (Teleostei: Ostariophysi: Characiformes) based on multilocus analysis and extensive ingroup sampling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação de Hb A2 e Hb F em doadores de sangue de região malarígena da Amazônia Oriental brasileira por HPLC

In malaria endemic regions of Africa, resistance to infection by Plasmodium has been observed in under 6-month-old children, when there are higher fetal hemoglobin (Hb F) levels. Research performed in the São José do Rio Preto region, central-east Brazil, reported increased levels of Hb F in blood donors. The purpose of this work was to evaluate the A2 hemoglobin (Hb A2) and Hb F concentrations in blood donors deriving from the Brazilian malaria endemic region. Forty-five blood donor samples from Macapá, from patients with varying genders, ages and ethnic origins, were collected by venous puncture after informed consent was obtained. The samples were analyzed by High Performance Liquid Chromatography (HPLC) - System Variant (Bio-Rad). The HPLC demonstrated sensitivity and rapidity in the identification and measurement of the hemoglobins and gave precise results. Moreover, it provided measurement of hemoglobin variants, even when they were present in small amounts, providing a diagnosis of hemoglobinopathies. Hb F levels above the normal were observed in 33.3% of the analyzed samples. The presence of increased Hb F can suggest resistance to infection by Plasmodium falciparum, as there have been reports that infected red blood cells interfere in the development of the parasite.

Atividade anti-inflamatória intestinal do extrato padronizado de Physalis angulata L. (camapú)

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

Dentes de Amniotas da Laje do Coringa (Formação Alcântara, albo-cenomaniano da bacia de São Luís-Grajaú): Identificação, descrição, aspectos paleobiológicos, biocronológicos, paleogeográficos e paleobiogeográficos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A diplomacia dos petrodólares: relações do Brasil com o mundo árabe (1973-1985)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O genocídio de Ruanda e a dinâmica da inação estadunidense

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)