Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice

Establishment of a community managed marine reserve in the Bay of Ranobe, southwest Madagascar

The Bay of Ranobe, in southwest Madagascar, once noted for its high biodiversity and fish abundance, is under increasing pressure from overfishing, pollution, sedimentation and tourism. The declining health of the coral reef is reflected in fishery productivity and survey data on biological diversity. Sustainable conservation requires the engagement of all interested parties and the integration of their needs into resource management. The British NGO ReefDoctor has adopted this approach in establishing the first community-protected site in the Bay of Ranobe, the Massif des Roses. This is a large coral patch with a high percentage of live coral cover (38%) and important fish diversity compared to other sites surveyed in the lagoon. Since 25 May 2007 it has been legally recognised as a community managed marine reserve under temporary protection where fishing is banned. Tourists must now pay an entry fee to visit the site, with the proceeds contributing to the funding of community projects. In conjunction with the protection of this site, ReefDoctor has worked with local people, regional and local government, tour operators and hotels, and conservation organisations to set up ‘FIMIHARA’, an association representative of local people responsible for the management of this site and the development of sustainable conservation initiatives in the Bay of Ranobe. This paper explains the approach taken by ReefDoctor, by setting up and working with FIMIHARA, to protect the Massif des Roses site and develop other conservation initiatives and community projects in the Bay of Ranobe. RÉSUMÉ La baie de Ranobe, au sud-ouest de Madagascar, autrefois remarquable pour sa biodiversité et l’abondance de la pêche, est de plus en plus menacée par la surpêche, la sédimentation, la pollution et le tourisme. Le déclin de l’état de santé du récif corallien se reflète dans la diminution de la productivité des pêcheries et dans les suivis de la biodiversité marine. La situation est à présent critique car les ressources marines associées au récif assurent la subsistance des populations côtières vivant le long de la baie. Nous considérons ici qu’une protection pérenne nécessite un engagement concret de toutes les parties prenantes - en particulier des communautés locales - et que leurs besoins soient intégrés dans la gestion des ressources. L’ONG ReefDoctor a mis en oeuvre cette approche lors de la création de la première réserve marine dans la baie de Ranobe gérée par la communauté locale, le Massif des Roses. Cette réserve est constituée d’un grand massif de corail largement couvert de coraux et abritant une importante diversité de poissons par rapport au reste du lagon. Depuis le 25 mai 2007, ce site est légalement reconnu comme réserve marine communautaire avec un statut de protection temporaire ; la pêche et les pratiques destructrices associées au tourisme y sont interdites. De plus, les touristes doivent désormais payer un droit d’entrée pour visiter le site, qui contribue au financement de projets communautaires. En parallèle avec la protection du site, ReefDoctor a travaillé avec les communautés locales, les responsables nationaux et régionaux du gouvernement, les opérateurs touristiques et diverses organisations de protection de la nature pour créer l’association FIMIHARA, représentative de la population locale. Cette association, qui a un statut légal depuis le 11 avril 2007, a pour but d’améliorer la qualité de vie de ceux qui vivent le long de la baie de Ranobe et de mettre en oeuvre des projets de conservation des ressources marines et terrestres dans la région de la baie de Ranobe. La création de la réserve marine communautaire du Massif des Roses a rapidement connu le succès qui s’est traduit par la vente de plus d’un millier de tickets, mais l’association FIMIHARA doit encore faire face à de nombreux défis. L’objectif principal de l’association à long terme est de développer son indépendance par rapport à l’ONG ReefDoctor et sa capacité à gérer indépendamment les ressources marines de la baie de Ranobe dont les communautés locales dépendent pour leur survie

Cryptic Diversity in Indo-Pacific Coral-Reef Fishes Revealed by DNA-Barcoding Provides New Support to the Centre-of-Overlap Hypothesis

Diversity in coral reef fishes is not evenly distributed and tends to accumulate in the Indo-Malay-Philippines Archipelago (IMPA). The comprehension of the mechanisms that initiated this pattern is in its infancy despite its importance for the conservation of coral reefs. Considering the IMPA either as an area of overlap or a cradle of marine biodiversity, the hypotheses proposed to account for this pattern rely on extant knowledge about taxonomy and species range distribution. The recent large-scale use of standard molecular data (DNA barcoding), however, has revealed the importance of taking into account cryptic diversity when assessing tropical biodiversity. We DNA barcoded 2276 specimens belonging to 668 coral reef fish species through a collaborative effort conducted concomitantly in both Indian and Pacific oceans to appraise the importance of cryptic diversity in species with an Indo-Pacific distribution range. Of the 141 species sampled on each side of the IMPA, 62 presented no spatial structure whereas 67 exhibited divergent lineages on each side of the IMPA with K2P distances ranging between 1% and 12%, and 12 presented several lineages with K2P distances ranging between 3% and 22%. Thus, from this initial pool of 141 nominal species with Indo-Pacific distribution, 79 dissolved into 165 biological units among which 162 were found in a single ocean. This result is consistent with the view that the IMPA accumulates diversity as a consequence of its geological history, its location on the junction between the two main tropical oceans and the presence of a land bridge during glacial times in the IMPA that fostered allopatric divergence and secondary contacts between the Indian and Pacific oceans

Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice

Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ−/− (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia

Modified Posterior Approach to Total Hip Arthroplasty to Enhance Joint Stability

We modified the posterior approach by preserving the external rotator muscles to enhance joint stability after primary THA. We asked whether this modified posterior approach would have a lower dislocation rate than the conventional posterior approach, with and without a repair of external rotator muscles. We retrospectively divided 557 patients (670 hips) who had undergone primary THA into three groups based on how the external rotator muscles had been treated during surgery: (1) not repaired after sectioning, (2) repaired after sectioning, or (3) not sectioned and preserved. The minimum followup was 1 year. In the group with preserved external rotator muscles, we observed no dislocations; in comparison, the dislocation rates for the repaired rotator group and the no-repair group were 3.9% and 5.3%, respectively. This modified posterior approach, which preserves the short external rotator muscles, seemed effective in preventing early dislocation after primary THA

Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice