High heterotrophic CO<Subscript>2</Subscript> emissions from a Malaysian oil palm plantations during dry-season

Tropical peatlands are currently being rapidly cleared and drained for the establishment of oil palm plantations, which threatens their globally significant carbon sequestration capacity. Large-scale land conversion of tropical peatlands is important in the context of greenhouse gas emission factors and sustainable land management. At present, quantification of carbon dioxide losses from tropical peatlands is limited by our understanding of the relative contribution of heterotrophic and autotrophic respiration to net peat surface CO₂ emissions. In this study we separated heterotrophic and autotrophic components of peat CO₂ losses from two oil palm plantations (one established in ‘2000’ and the other in 1978, then replanted in ‘2006’) using chamber-based emissions sampling along a transect from the rooting to non-rooting zones on a peatland in Selangor, Peninsular Malaysia over the course of 3 months (June–August, 2014). Collar CO₂ measurements were compared with soil temperature and moisture at site and also accompanied by depth profiles assessing peat C and bulk density. The soil respiration decreased exponentially with distance from the palm trunks with the sharpest decline found for the plantation with the younger palms with overall fluxes of 1341 and 988 mg CO₂ m^?2 h^?1, respectively, at the 2000 and 2006 plantations, respectively. The mean heterotrophic flux was 909 ± SE 136 and 716 ± SE 201 mg m^?2 h^?1 at the 2000 and 2006 plantations, respectively. Autotrophic emissions adjacent to the palm trunks were 845 ± SE 135 and 1558 ± SE 341 mg m^?2 h^?1 at the 2000 and 2006 plantations, respectively. Heterotrophic CO₂ flux was positively related to peat soil moisture, but not temperature. Total peat C stocks were 60 kg m^?2 (down to 1 m depth) and did not vary among plantations of different ages but SOC concentrations declined significantly with depth at both plantations but the decline was sharper in the second generation 2006 plantation. The CO₂ flux values reported in this study suggest a potential for very high carbon (C) loss from drained tropical peats during the dry season. This is particularly concerning given that more intense dry periods related to climate change are predicted for SE Asia. Taken together, this study highlights the need for careful management of tropical peatlands, and the vulnerability of their carbon storage capability under conditions of drainage.     

Effects Of Vegetation and Soil on Species Diversity of Soil Dwelling Diptera in a Heathland Ecosystem

The role of vegetation and soil factors on the biodiversity of two soil dwelling, saprophagous, fly families (Sphaeroceridae and Lonchopteridae) in a heathland ecosystem were investigated. The fly community is primarily affected by soil humidity and the amount of organic matter while the vegetation structure and species composition only indirectly influence the fly communities. There was no correlation between plant species richness and the fly diversity indices. Based on our results and literature data, we hypothesise that the direct effects of the vegetation is more evident for herbivorous insects than for species that do not feed on plants. The investigated families show a clear response to microhabitat differences in the soil factors, which makes them promising indicators for soil health and as tool for monitoring environmental changes.     

Tumor necrosis factor inhibits glucocorticoid receptor function in mice: a strong signal toward lethal shock

As glucocorticoid resistance (GCR) and the concomitant burden pose a worldwide problem, there is an urgent need for a more effective glucocorticoid therapy, for which insights into the molecular mechanisms of GCR are essential. In this study, we addressed the hypothesis that TNFα, a strong pro-inflammatory mediator in numerous inflammatory diseases, compromises the protective function of the glucocorticoid receptor (GR) against TNFα-induced lethal inflammation. Indeed, protection of mice by dexamethasone against TNFα lethality was completely abolished when it was administered after TNFα stimulation, indicating compromised GR function upon TNFα challenge. TNFα-induced GCR was further demonstrated by impaired GR-dependent gene expression in the liver. Furthermore, TNFα down-regulates the levels of both GR mRNA and protein. However, this down-regulation seems to occur independently of GC production, as TNFα also resulted in down-regulation of GR levels in adrenalectomized mice. These findings suggest that the decreased amount of GR determines the GR response and outcome of TNFα-induced shock, as supported by our studies with GR heterozygous mice. We propose that by inducing GCR, TNFα inhibits a major brake on inflammation and thereby amplifies the pro-inflammatory response. Our findings might prove helpful in understanding GCR in inflammatory diseases in which TNFα is intimately involved.     

Immunomodulatory drugs improve the immune environment for dendritic cell-based immunotherapy in multiple myeloma patients after autologous stem cell transplantation

Multiple myeloma (MM) is characterized by a malignant proliferation of plasma cells in the bone marrow with associated organ damage. Although the prognosis of MM has improved recently, the disease remains incurable for the large majority of patients. The eradication of residual disease in the bone marrow is a main target on the road toward cure. Immune cells play a role in the control of cancer and can be tools to attack residual MM cells. However, the myeloma-associated immune deficiency is a major hurdle to immunotherapy. We evaluated ex vivo the effects of low doses of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide on several immune cell types from MM patients after autologous stem cell transplantation and with low tumor burden. We observed that these drugs increased CD4⁺ and CD8⁺ T-cell proliferation and cytokine production, enhanced the lytic capacity of cytotoxic T lymphocytes and reduced the suppressive effects of regulatory T cells on CD8⁺ T-cell responses. In addition, we found that functional dendritic cells (DCs) can be generated from mononuclear cells from MM patients. The presence of IMiDs improved the quality of antigen-specific T cells induced or expanded by these DCs as evidenced by a higher degree of T-cell polyfunctionality. Our results provide a rationale for the design of early phase clinical studies to assess the efficacy of DC-based immunotherapy in combination with posttransplant maintenance treatment with IMiDs in MM.     

Peroxisome Dynamics in Cultured Mammalian Cells

Despite the identification and characterization of various proteins that are essential for peroxisome biogenesis, the origin and the turnover of peroxisomes are still unresolved critical issues. In this study, we used the HaloTag technology as a new approach to examine peroxisome dynamics in cultured mammalian cells. This technology is based on the formation of a covalent bond between the HaloTag protein–a mutated bacterial dehalogenase which is fused to the protein of interest–and a synthetic haloalkane ligand that contains a fluorophore or affinity tag. By using cell-permeable ligands of distinct fluorescence, it is possible to image distinct pools of newly synthesized proteins, generated from a single genetic HaloTag-containing construct, at different wavelengths. Here, we show that peroxisomes display an age-related heterogeneity with respect to their capacity to incorporate newly synthesized proteins. We also demonstrate that these organelles do not exchange their protein content. In addition, we present evidence that the matrix protein content of pre-existing peroxisomes is not evenly distributed over new organelles. Finally, we show that peroxisomes in cultured mammalian cells, under basal growth conditions, have a half-life of approximately 2 days and are mainly degraded by an autophagy-related mechanism. The implications of these findings are discussed.     

Hippocampal disruptions of synaptic and astrocyte metabolism are primary events of early amyloid pathology in the 5xFAD mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, this crucial metabolic interplay during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in the 5xFAD hippocampus. This hyperactive neuronal phenotype coincided with decreased hippocampal tricarboxylic acid (TCA) cycle metabolism mapped by stable ¹³C isotope tracing. Particularly, reduced astrocyte TCA cycle activity and decreased glutamine synthesis led to hampered neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, the cerebral cortex of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism, which may suggest a metabolic compensation in this brain region. We found limited changes when we explored the brain proteome and metabolome of the 5xFAD mice, supporting that the functional metabolic disturbances between neurons and astrocytes are early primary events in AD pathology. In addition, synaptic mitochondrial and glycolytic function was selectively impaired in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex regional and cell-specific metabolic adaptations in the early stages of amyloid pathology, which may be fundamental for the progressing synaptic dysfunctions in AD.Subject terms: Proteomics, Alzheimer''s disease, Molecular neuroscience, Alzheimer''s disease