314 research outputs found

    Response of carbon fluxes to water relations in a savanna ecosystem in South Africa

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    International audienceThe principal mechanisms that connect carbon fluxes with water relations in savanna ecosystems were studied by using eddy covariance in a savanna ecosystem at Kruger National Park, South Africa. Since the annual drought and rewetting cycle is a major factor influencing the function of savanna ecosystems, this work focused on the close inter-connection between water relations and carbon fluxes. Data from a nine-month measuring campaign lasting from the early wet season to the late dry season were used. Total ecosystem respiration showed highest values at the onset of the growing season, a slightly lower plateau during the main part of the growing season and a continuous decrease during the transition towards the dry season. The regulation of canopy conductance was changed in two ways: changes due to phenology during the course of the growing season and short-term acclimation to soil water conditions. The most constant parameter was water use efficiency that was influenced by VPD during the day but the VPD response curve of water usage did change only slightly during the course of the growing season and decreased by about 30% during the transition from wet to dry season. The regulation of canopy conductance and photosynthetic capacity were closely related. This observation meets recent leaf-level findings that stomatal closure triggers down-regulation of Rubisco during drought. Our results may show the effects of these processes on the ecosystem scale

    Sensitizing Protective Tumor Microenvironments to Antibody-Mediated Therapy

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    Therapy-resistant microenvironments represent a major barrier toward effective elimination of disseminated malignancies. Here, we show that select microenvironments can underlie resistance to antibody-based therapy. Using a humanized model of treatment refractory B cell leukemia, we find that infiltration of leukemia cells into the bone marrow rewires the tumor microenvironment to inhibit engulfment of antibody-targeted tumor cells. Resistance to macrophage-mediated killing can be overcome by combination regimens involving therapeutic antibodies and chemotherapy. Specifically, the nitrogen mustard cyclophosphamide induces an acute secretory activating phenotype (ASAP), releasing CCL4, IL8, VEGF, and TNFα from treated tumor cells. These factors induce macrophage infiltration and phagocytic activity in the bone marrow. Thus, the acute induction of stress-related cytokines can effectively target cancer cells for removal by the innate immune system. This synergistic chemoimmunotherapeutic regimen represents a potent strategy for using conventional anticancer agents to alter the tumor microenvironment and promote the efficacy of targeted therapeutics.Massachusetts Institute of Technology. Ludwig Center for Molecular OncologyKathy and Curt Marble Cancer Research FundSingapore-MIT Alliance for Research and TechnologyGerman Research Foundation (KFO286)German Research Foundation (Fellowship)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051

    Complexity in water and carbon dioxide fluxes following rain pulses in an African savanna

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    The idea that many processes in arid and semi-arid ecosystems are dormant until activated by a pulse of rainfall, and then decay from a maximum rate as the soil dries, is widely used as a conceptual and mathematical model, but has rarely been evaluated with data. This paper examines soil water, evapotranspiration (ET), and net ecosystem CO2 exchange measured for 5 years at an eddy covariance tower sited in an Acacia–Combretum savanna near Skukuza in the Kruger National Park, South Africa. The analysis characterizes ecosystem flux responses to discrete rain events and evaluates the skill of increasingly complex “pulse models”. Rainfall pulses exert strong control over ecosystem-scale water and CO2 fluxes at this site, but the simplest pulse models do a poor job of characterizing the dynamics of the response. Successful models need to include the time lag between the wetting event and the process peak, which differ for evaporation, photosynthesis and respiration. Adding further complexity, the time lag depends on the prior duration and degree of water stress. ET response is well characterized by a linear function of potential ET and a logistic function of profile-total soil water content, with remaining seasonal variation correlating with vegetation phenological dynamics (leaf area). A 1- to 3-day lag to maximal ET following wetting is a source of hysteresis in the ET response to soil water. Respiration responds to wetting within days, while photosynthesis takes a week or longer to reach its peak if the rainfall was preceded by a long dry spell. Both processes exhibit nonlinear functional responses that vary seasonally. We conclude that a more mechanistic approach than simple pulse modeling is needed to represent daily ecosystem C processes in semiarid savannas

    Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals

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    Chemokines influence HIV neuropathogenesis by affecting the HIV life cycle, trafficking of macrophages into the nervous system, glial activation, and neuronal signaling and repair processes; however, knowledge of their relationship to in vivo measures of cerebral injury is limited. The primary objective of this study was to determine the relationship between a panel of chemokines in cerebrospinal fluid (CSF) and cerebral metabolites measured by proton magnetic resonance spectroscopy (MRS) in a cohort of HIV-infected individuals. One hundred seventy-one stored CSF specimens were assayed from HIV-infected individuals who were enrolled in two ACTG studies that evaluated the relationship between neuropsychological performance and cerebral metabolites. Concentrations of six chemokines (fractalkine, IL-8, IP-10, MCP-1, MIP-1β, and SDF-1) were measured and compared with cerebral metabolites individually and as composite neuronal, basal ganglia, and inflammatory patterns. IP-10 and MCP-1 were the chemokines most strongly associated with individual cerebral metabolites. Specifically, (1) higher IP-10 levels correlated with lower N-acetyl aspartate (NAA)/creatine (Cr) ratios in the frontal white matter and higher MI/Cr ratios in all three brain regions considered and (2) higher MCP-1 levels correlated with lower NAA/Cr ratios in frontal white matter and the parietal cortex. IP-10, MCP-1, and IL-8 had the strongest associations with patterns of cerebral metabolites. In particular, higher levels of IP-10 correlated with lower neuronal pattern scores and higher basal ganglia and inflammatory pattern scores, the same pattern which has been associated with HIV-associated neurocognitive disorders (HAND). Subgroup analysis indicated that the effects of IP-10 and IL-8 were influenced by effective antiretroviral therapy and that memantine treatment may mitigate the neuronal effects of IP-10. This study supports the role of chemokines in HAND and the validity of MRS as an assessment tool. In particular, the findings identify relationships between the immune response—particularly an interferon-inducible chemokine, IP-10—and cerebral metabolites and suggest that antiretroviral therapy and memantine modify the impact of the immune response on neurons

    Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 2: Untangling climatic, edaphic, management and nitrogen deposition effects on carbon sequestration potentials

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    The effects of atmospheric nitrogen deposition (Ndep_{dep}) on carbon (C) sequestration in forests have often been assessed by relating differences in productivity to spatial variations of Ndep_{dep} across a large geographic domain. These correlations generally suffer from covariation of other confounding variables related to climate and other growth-limiting factors, as well as large uncertainties in total (dry+wet) reactive nitrogen (Nr_{r}) deposition.We propose a methodology for untangling the effects of Ndep_{dep} from those of meteorological variables, soil water retention capacity and stand age, using a mechanistic forest growth model in combination with eddy covariance CO2_{2} exchange fluxes from a Europe-wide network of 22 forest flux towers. Total Nr_{r} deposition rates were estimated from local measurements as far as possible. The forest data were compared with data from natural or semi-natural, non-woody vegetation sites. The response of forest net ecosystem productivity to nitrogen deposition (dNEP= dNdep_{dep}) was estimated after accounting for the effects on gross primary productivity (GPP) of the co-correlates by means of a meta-modelling standardization procedure, which resulted in a reduction by a factor of about 2 of the uncorrected, apparent dGPP/dNdep_{dep} value. This model-enhanced analysis of the C and Ndep_{dep} flux observations at the scale of the European network suggests a mean overall dNEP/dNdep_{dep} response of forest lifetime C sequestration to Ndep_{dep} of the order of 40–50 g C per g N, which is slightly larger but not significantly different from the range of estimates published in the most recent reviews. Importantly, patterns of gross primary and net ecosystem productivity versus Ndep_{dep} were non-linear, with no further growth responses at high Ndep_{dep} levels (Ndep_{dep} >2.5–3 gNm2^{-2} yr1^{-1}) but accompanied by increasingly large ecosystem N losses by leaching and gaseous emissions. The reduced increase in productivity per unit N deposited at high Ndep_{dep} levels implies that the forecast increased Nr_{r} emissions and increased Ndep levels in large areas of Asia may not positively impact the continent’s forest CO2_{2} sink. The large level of unexplained variability in observed carbon sequestration efficiency (CSE) across sites further adds to the uncertainty in the dC/dN response

    Perturbation of Host Nuclear Membrane Component RanBP2 Impairs the Nuclear Import of Human Immunodeficiency Virus -1 Preintegration Complex (DNA)

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    HIV-1 is a RNA virus that requires an intermediate DNA phase via reverse transcription (RT) step in order to establish productive infection in the host cell. The nascent viral DNA synthesized via RT step and the preformed viral proteins are assembled into pre-integration complex (PIC) in the cell cytoplasm. To integrate the viral DNA into the host genome, the PIC must cross cell nuclear membrane through the nuclear pore complex (NPC). RanBP2, also known as Nup358, is a major component of the cytoplasmic filaments that emanates from the nuclear pore complex and has been implicated in various nucleo-cytoplasmic transport pathways including those for HIV Rev-protein. We sought to investigate the role of RanBP2 in HIV-1 replication. In our investigations, we found that RanBP2 depletion via RNAi resulted in profound inhibition of HIV-1 infection and played a pivotal role in the nuclear entry of HIV DNA. More precisely, there was a profound decline in 2-LTR DNA copies (marker for nuclear entry of HIV DNA) and an unchanged level of viral reverse transcription in RanBP2-ablated HIV-infected cells compared to RanBP3-depleted or non-specific siRNA controls. We further demonstrated that the function of Rev was unaffected in RanBP2-depleted latently HIV infected cells (reactivated). We also serendipitously found that RanBP2 depletion inhibited the global ectopic gene expression. In conclusion, RanBP2 is a host factor that is involved in the nuclear import of HIV-1 PIC (DNA), but is not critical to the nuclear export of the viral mRNAs or nucleo-cytoplasmic shuttling of Rev. RanBP2 could be a potential target for efficient inhibition of HIV
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