Sustainable Livelihoods Enhancement and Diversification (SLED): A Manual for Practitioners

The aim of this document is to provide development practitioners with an introduction to the SLED process as well as guidance for practitioners facilitating that process. The Sustainable Livelihoods Enhancement and Diversification (SLED) approach has been developed by Integrated Marine Management Ltd (IMM) through building on the lessons of past livelihoods research projects as well as worldwide experience in livelihood improvement and participatory development practice. It aims to provide a set of guidelines for development and conservation practitioners whose task it is to assist people in enhancing and diversifying their livelihoods. Under the Coral Reefs and Livelihoods Initiative (CORALI), this approach has been field tested and further developed in very different circumstances and institutional settings, in six sites across South Asia and Indonesia. While this process of testing and refining SLED has been carried out specifically in the context of efforts to manage coastal and marine resources, it is an approach that can be applied widely wherever natural resources are facing degradation because of unsustainable human use. The SLED approach provides a framework within which diverse local contexts and the local complexities of livelihood change can be accommodated

In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia

We recently reported that rabbit antithymocyte globulin was markedly inferior to horse antithymocyte globulin as a primary treatment for severe aplastic anemia. Here we expand on our findings in this unique cohort of patients. Rabbit antithymocyte globulin was detectable in plasma for longer periods than horse antithymocyte globulin; rabbit antithymocyte globulin in plasma retained functional capacity to bind to lymphocytes for up to 1 month, horse antithymocyte globulin for only about 2 weeks. In the first week after treatment there were much lower numbers of neutrophils in patients treated with rabbit antithymocyte globulin than in patients receiving horse antithymocyte globulin. Both antithymocyte globulins induced a “cytokine storm” in the first 2 days after administration. Compared with horse antithymocyte globulin, rabbit antithymocyte globulin was associated with higher levels of chemokine (C-C motif) ligand 4 during the first 3 weeks. Besides a much lower absolute number and a lower relative frequency of CD4(+) T cells, rabbit antithymocyte globulin induced higher frequencies of CD4(+)CD38(+), CD3(+)CD4(−)CD8(−) T cells, and B cells than did horse antithymocyte globulin. Serum sickness occurred around 2 weeks after infusion of both types of antithymocyte globulin. Human anti-antithymocyte globulin antibodies, especially of the IgM subtype, correlated with serum sickness, which appeared concurrently with clearance of antithymocyte globulin in blood and with the production of cytokines. In conclusion, rabbit and horse antithymocyte globulins have very different pharmacokinetics and effects on neutrophils, lymphocyte subsets, and cytokine release. These differences may be related to their efficacy in suppressing the immune system and restoring hematopoiesis in bone marrow failure. Clinicaltrials.gov identifier: NCT00260689

Neutralising immunity to omicron sublineages BQ.1.1, XBB, and XBB.1.5 in healthy adults is boosted by bivalent BA.1-containing mRNA vaccination and previous Omicron infection

The global COVID-19 landscape is increasingly complex; emerging new variants rapidly cause waves of infection in people with variably induced immunity. Most individuals now have so-called hybrid immunity from both infection and vaccination. However, sequential infecting variants, induction of immunity, and subsequent waning are interlinked, and immune protection against new variants is unclear

A Differential Role for Macropinocytosis in Mediating Entry of the Two Forms of Vaccinia Virus into Dendritic Cells

Vaccinia virus (VACV) is being developed as a recombinant viral vaccine vector for several key pathogens. Dendritic cells (DCs) are specialised antigen presenting cells that are crucial for the initiation of primary immune responses; however, the mechanisms of uptake of VACV by these cells are unclear. Therefore we examined the binding and entry of both the intracellular mature virus (MV) and extracellular enveloped virus (EV) forms of VACV into vesicular compartments of monocyte-derived DCs. Using a panel of inhibitors, flow cytometry and confocal microscopy we have shown that neither MV nor EV binds to the highly expressed C-type lectin receptors on DCs that are responsible for capturing many other viruses. We also found that both forms of VACV enter DCs via a clathrin-, caveolin-, flotillin- and dynamin-independent pathway that is dependent on actin, intracellular calcium and host-cell cholesterol. Both MV and EV entry were inhibited by the macropinocytosis inhibitors rottlerin and dimethyl amiloride and depended on phosphotidylinositol-3-kinase (PI(3)K), and both colocalised with dextran but not transferrin. VACV was not delivered to the classical endolysosomal pathway, failing to colocalise with EEA1 or Lamp2. Finally, expression of early viral genes was not affected by bafilomycin A, indicating that the virus does not depend on low pH to deliver cores to the cytoplasm. From these collective results we conclude that VACV enters DCs via macropinocytosis. However, MV was consistently less sensitive to inhibition and is likely to utilise at least one other entry pathway. Definition and future manipulation of these pathways may assist in enhancing the activity of recombinant vaccinia vectors through effects on antigen presentation

2009

ABSTRACT Method

Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia.

再生不良性貧血における遺伝子変異の解明 -白血病発症にいたる過程を初めて解明-. 京都大学プレスリリース. 2015-07-09.[BACKGROUND]In patients with acquired aplastic anemia, destruction of hematopoietic cells by the immune system leads to pancytopenia. Patients have a response to immunosuppressive therapy, but myelodysplastic syndromes and acute myeloid leukemia develop in about 15% of the patients, usually many months to years after the diagnosis of aplastic anemia. [METHODS]We performed next-generation sequencing and array-based karyotyping using 668 blood samples obtained from 439 patients with aplastic anemia. We analyzed serial samples obtained from 82 patients. [RESULTS]Somatic mutations in myeloid cancer candidate genes were present in one third of the patients, in a limited number of genes and at low initial variant allele frequency. Clonal hematopoiesis was detected in 47% of the patients, most frequently as acquired mutations. The prevalence of the mutations increased with age, and mutations had an age-related signature. DNMT3A-mutated and ASXL1-mutated clones tended to increase in size over time; the size of BCOR- andBCORL1-mutated and PIGA-mutated clones decreased or remained stable. Mutations in PIGA and BCOR and BCORL1 correlated with a better response to immunosuppressive therapy and longer and a higher rate of overall and progression-free survival; mutations in a subgroup of genes that included DNMT3A and ASXL1 were associated with worse outcomes. However, clonal dynamics were highly variable and might not necessarily have predicted the response to therapy and long-term survival among individual patients. [CONCLUSIONS]Clonal hematopoiesis was prevalent in aplastic anemia. Some mutations were related to clinical outcomes. A highly biased set of mutations is evidence of Darwinian selection in the failed bone marrow environment. The pattern of somatic clones in individual patients over time was variable and frequently unpredictable. (Funded by Grant-in-Aid for Scientific Research and others.