Global land use implications of biofuels: State of the art conference and workshop on modelling global land use implications in the environmental assessment of biofuels

Background, Aims and Scope On 4¿5 June 2007, an international conference was held in Copenhagen. It provided an interdisciplinary forum where economists and geographers met with LCA experts to discuss the challenges of modelling the ultimate land use changes caused by an increased demand for biofuels. Main Features The main feature of the conference was the cross-breeding of experience from the different approaches to land use modelling: The field of LCA could especially benefit from economic modelling in the identification of marginal crop production and the resulting expansion of the global agricultural area. Furthermore, the field of geography offers insights in the complexity behind new land cultivation and practical examples of where this is seen to occur on a regional scale. Results Results presented at the conference showed that the magnitude and location of land use changes caused by biofuels demand depend on where the demand arises. For instance, mandatory blending in the EU will increase land use both within and outside of Europe, especially in South America. A key learning for the LCA society was that the response to a change in demand for a given crop is not presented by a single crop supplier or a single country, but rather by responses from a variety of suppliers of several different crops in several countries. Discussion The intensification potential of current and future crop and biomass production was widely discussed. It was generally agreed that some parts of the third world hold large potentials for intensification, which are not realised due to a number of barriers resulting in so-called yield gaps. Conclusions Modelling the global land use implications of biofuels requires an interdisciplinary approach optimally integrating economic, geographical, biophysical, social and possibly other aspects in the modelling. This interdisciplinary approach is necessary but also difficult due to different perspectives and mindsets in the different disciplines. Recommendations and Perspectives The concept of a location dependent marginal land use composite should be introduced in LCA of biofuels and it should be acknowledged that the typical LCA assumption of linear substitution is not necessarily valid. Moreover, fertiliser restrictions/accessibility should be included in land use modelling and the relation between crop demand and intensification should be further explored. In addition, environmental impacts of land use intensification should be included in LCA, the powerful concept of land use curves should be further improved, and so should the modelling of diminishing returns in crop production

Cytomegalovirus-mediated T cell receptor repertoire perturbation is present in early life

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus, particularly in sub-Saharan Africa, where it is endemic from infancy. The T cell response against CMV is important in keeping the virus in check, with CD8 T cells playing a major role in the control of CMV viraemia. Human leukocyte antigen (HLA) B*44:03-positive individuals raise a robust response against the NEGVKAAW (NW8) epitope, derived from the immediate-early-2 (IE-2) protein. We previously showed that the T cell receptor (TCR) repertoire raised against the NW8-HLA-B*44:03 complex was oligoclonal and characterised by superdominant clones, which were shared amongst unrelated individuals (i.e., “public”). Here, we address the question of how stable the CMV-specific TCR repertoire is over the course of infection, and whether substantial differences are evident in TCR repertoires in children, compared with adults. We present a longitudinal study of four HIV/CMV co-infected mother-child pairs, who in each case express HLA-B*44:03 and make responses to the NW8 epitope, and analyse their TCR repertoire over a period spanning more than 10 years. Using high-throughput sequencing, the paediatric CMV-specific repertoire was found to be highly diverse. In addition, paediatric repertoires were remarkably similar to adults, with public TCR responses being shared amongst children and adults alike. The CMV-specific repertoire in both adults and children displayed strong fluctuations in TCR clonality and repertoire architecture over time. Previously characterised superdominant clonotypes were readily identifiable in the children at high frequency, suggesting that the distortion of the CMV-specific repertoire is incurred as a direct result of CMV infection rather than a product of age-related “memory inflation.” Early distortion of the TCR repertoire was particularly apparent in the case of the TCR-β chain, where oligoclonality was low in children and positively correlated with age, a feature we did not observe for TCR-α. This discrepancy between TCR-α and -β chain repertoire may reflect differential contribution to NW8 recognition. Altogether, the results of the present study provide insight into the formation of the TCR repertoire in early life and pave the way to better understanding of CD8 T cell responses to CMV at the molecular level

A simple, robust flow cytometry-based whole blood assay for investigating sex differential interferon alpha production by plasmacytoid dendritic cells

Central to sex differences observed in outcome from infection and vaccination is the innate immune response, and specifically production of type I interferons by plasmacytoid dendtiric cells (pDCs), the main producers of IFN-α. Evaluation of IFN-α production by pDCs is therefore critical for studies of innate immune function. However, reliable measurement of pDC IFN-α is hampered by reduced cell yields and cytokine production after cryopreservation or after even short delays in stimulating freshly isolated cells. We here describe a simple yet robust method for measuring IFN-α production in pDCs that preserves cell activation and cytokine production through immediate stimulation of whole blood and subsequent maintenance at 37 °C

Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy

Innate lymphoid cells (ILCs) are important for response to infection and for immune development in early life. HIV infection in adults depletes circulating ILCs, but the impact on children infected from birth remains unknown. We study vertically HIV-infected children from birth to adulthood and find severe and persistent depletion of all circulating ILCs that, unlike CD4+ T cells, are not restored by long-term antiretroviral therapy unless initiated at birth. Remaining ILCs upregulate genes associated with cellular activation and metabolic perturbation. Unlike HIV-infected adults, ILCs are also profoundly depleted in tonsils of vertically infected children. Transcriptional profiling of remaining ILCs reveals ongoing cell-type-specific activity despite antiretroviral therapy. Collectively, these data suggest an important and ongoing role for ILCs in lymphoid tissue of HIV-infected children from birth, where persistent depletion and sustained transcriptional activity are likely to have long-term immune consequences that merit further investigation

Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection

HIV infection in the human gastrointestinal (GI) tract is thought to be central to HIV progression, but knowledge of this interaction is primarily limited to cohorts within Westernized countries. Here, we present a large cohort recruited from high HIV endemic areas in South Africa and found that people living with HIV (PLWH) presented at a younger age for investigation in the GI clinic. We identified severe CD4(+) T cell depletion in the GI tract, which was greater in the small intestine than in the large intestine and not correlated with years on antiretroviral treatment (ART) or plasma viremia. HIV-p24 staining showed persistent viral expression, particularly in the colon, despite full suppression of plasma viremia. Quantification of mucosal antiretroviral (ARV) drugs revealed no differences in drug penetration between the duodenum and colon. Plasma markers of gut barrier breakdown and immune activation were elevated irrespective of HIV, but peripheral T cell activation was inversely correlated with loss of gut CD4(+) T cells in PLWH alone. T cell activation is a strong predictor of HIV progression and independent of plasma viral load, implying that the irreversible loss of GI CD4(+) T cells is a key event in the HIV pathogenesis of PLWH in South Africa, yet the underlying mechanisms remain unknown

Increased Regulatory T-Cell Activity and Enhanced T-Cell Homeostatic Signaling in Slow Progressing HIV-infected Children

Pediatric slow progressors (PSP) are rare ART-naïve, HIV-infected children who maintain high CD4 T-cell counts and low immune activation despite persistently high viral loads. Using a well-defined cohort of PSP, we investigated the role of regulatory T-cells (TREG) and of IL-7 homeostatic signaling in maintaining normal-for-age CD4 counts in these individuals. Compared to children with progressive disease, PSP had greater absolute numbers of TREG, skewed toward functionally suppressive phenotypes. As with immune activation, overall T-cell proliferation was lower in PSP, but was uniquely higher in central memory TREG (CM TREG), indicating active engagement of this subset. Furthermore, PSP secreted higher levels of the immunosuppressive cytokine IL-10 than children who progressed. The frequency of suppressive TREG, CM TREG proliferation, and IL-10 production were all lower in PSP who go on to progress at a later time-point, supporting the importance of an active TREG response in preventing disease progression. In addition, we find that IL-7 homeostatic signaling is enhanced in PSP, both through preserved surface IL-7receptor (CD127) expression on central memory T-cells and increased plasma levels of soluble IL-7receptor, which enhances the bioactivity of IL-7. Combined analysis, using a LASSO modeling approach, indicates that both TREG activity and homeostatic T-cell signaling make independent contributions to the preservation of CD4 T-cells in HIV-infected children. Together, these data demonstrate that maintenance of normal-for-age CD4 counts in PSP is an active process, which requires both suppression of immune activation through functional TREG, and enhanced T-cell homeostatic signaling

Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children

Background. Susceptibility to coinfections in human immunodefciency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specifc T-cell responses in children before and afer ART. Methods. We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)- specifc T-cell responses before and 1 year afer initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays afer in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses afer antigen stimulation. Results. We observed diferential, pathogen-specifc changes afer 1 year of ART in cytokine profles of CD4 T-cell responses that were associated with shifs in memory phenotype and decreased programmed cell death 1 (PD-1) expression. Te proliferative capacity of HIV- and PPD-specifc responses increased afer 1 year of ART. Of note, the recovery of CMV- and TB-specifc responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Conclusions. Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. Te PD-1 pathway represents a potential target for immunotherapy in HIVinfected patients on ART with insufcient immune reconstitution

Lobster Fishery Management in the Marine Ecosystem Approach at Simeulue Island Waters (Wpp-nri 572)

The lobster fishery is one of the leading fisheries commodity on Simeulue Regency so that local government must manage wisely in order to maintain the sustainability of the lobster fishery. Aceh Government Regulation namely Qanun Aceh No. 7 of 2010 concerning fisheries already in effect. However, the institutional system has not functioned optimally in the management of lobster fisheries. The purpose this study is to examine the domain of fishing techniques, socio-economic and institutional management of lobster fisheries with ecosystem approaches in Simeulue waters. Research method using qualitative research. The method of data collection is survey method which is done by purposive sampling approach that is by doing depth responder interview which is considered informative and wide knowledge about the institute. Data analysis using EAFM analysis done with Flag Modeling technique. Based on the results of the study that the assessment of the fishing domain techniques and economic domains in aggregate showed bad category. Meanwhile, social domains and institutional domains show moderate categories so aggregate composites overall show fewer categories. It is therefore necessary to make a tactical decision from the bad to be better in accordance with the category of each EAFM domain

Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children

Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group