Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis

Experimental autoimmune neuritis (EAN), an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system, is characterized by self-limitation. Here we investigated the regulation and contribution of erythropoietin (EPO) in EAN self-limitation. In EAN sciatic nerves, hypoxia, and protein and mRNA levels of hypoxia-inducible factor 1α (HIF-1α), HIF-2α, EPO and EPO receptor (EPOR) were induced in parallel at disease peak phase but reduced at recovery periods. Further, the deactivation of HIF reduced EAN-induced EPO/EPOR upregulation in EAN, suggesting the central contribution of HIF to EPO/EPOR induction. The deactivation of EPOR signalling exacerbated EAN progression, implying that endogenous EPO contributed to EAN recovery. Exogenous EPO treatment greatly improved EAN recovery. In addition, EPO was shown to promote Schwann cell survival and myelin production. In EAN, EPO treatment inhibited lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3⁺/CD4⁺ regulatory T cells and decrease of IFN-γ⁺/CD4⁺ Th1 cells. Furthermore, EPO inhibited inflammatory macrophage activation and promoted its phagocytic activity. In summary, our data demonstrated that EPO was induced in EAN by HIF and contributed to EAN recovery, and endogenous and exogenous EPO could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that EPO contributes to the self-recovery of EAN and could be a potent candidate for treatment of autoimmune neuropathies.     

Candidate genes and gene markers for the resistance to porcine pleuropneumonia

Mammalian Genome - Actinobacillus (A.) pleuropneumoniae is one of the most important respiratory pathogens in global pig production. Antimicrobial treatment and vaccination provide only limited...     

Wasteful,essential, evolutionary stepping stone? The multiple personalities of the photorespiratory pathway

The photorespiratory pathway, in short photorespiration, is a metabolic repair system that enables the CO₂ fixation enzyme Rubisco to sustainably operate in the presence of oxygen, that is, during oxygenic photosynthesis of plants and cyanobacteria. Photorespiration is necessary because an auto‐inhibitory metabolite, 2‐phosphoglycolate (2PG), is produced when Rubisco binds oxygen instead of CO₂ as a substrate and must be removed, to avoid collapse of metabolism, and recycled as efficiently as possible. The basic principle of recycling 2PG very likely evolved several billion years ago in connection with the evolution of oxyphotobacteria. It comprises the multi‐step combination of two molecules of 2PG to form 3‐phosphoglycerate. The biochemistry of this process dictates that one out of four 2PG carbons is lost as CO₂, which is a long‐standing plant breeders' concern because it represents by far the largest fraction of respiratory processes that reduce gross‐photosynthesis of major crops down to about 50% and less, lowering potential yields. In addition to the ATP needed for recycling of the 2PG carbon, extra energy is needed for the refixation of liberated equal amounts of ammonia. It is thought that the energy costs of photorespiration have an additional negative impact on crop yields in at least some environments. This paper discusses recent advances concerning the origin and evolution of photorespiration, and gives an overview of contemporary and envisioned strategies to engineer the biochemistry of, or even avoid, photorespiration.     

Electron availability in CO2, CO and H2 mixtures constrains flux distribution,energy management and product formation in Clostridium ljungdahlii

Acetogens such as Clostridium ljungdahlii can play a crucial role reducing the human CO₂ footprint by converting industrial emissions containing CO₂, CO and H₂ into valuable products such as organic acids or alcohols. The quantitative understanding of cellular metabolism is a prerequisite to exploit the bacterial endowments and to fine-tune the cells by applying metabolic engineering tools. Studying the three gas mixtures CO₂ + H₂, CO and CO + CO₂ + H₂ (syngas) by continuously gassed batch cultivation experiments and applying flux balance analysis, we identified CO as the preferred carbon and electron source for growth and producing alcohols. However, the total yield of moles of carbon (mol-C) per electrons consumed was almost identical in all setups which underlines electron availability as the main factor influencing product formation. The Wood–Ljungdahl pathway (WLP) showed high flexibility by serving as the key NAD⁺ provider for CO₂ + H_2, whereas this function was strongly compensated by the transhydrogenase-like Nfn complex when CO was metabolized. Availability of reduced ferredoxin (Fd_red) can be considered as a key determinant of metabolic control. Oxidation of CO via carbon monoxide dehydrogenase (CODH) is the main route of Fd_red formation when CO is used as substrate, whereas Fd_red is mainly regenerated via the methyl branch of WLP and the Nfn complex utilizing CO₂ + H₂. Consequently, doubled growth rates, highest ATP formation rates and highest amounts of reduced products (ethanol, 2,3-butanediol) were observed when CO was the sole carbon and electron source.     

The climate change mitigation effect of bioenergy from sustainably managed forests in Central Europe

We compare sustainably managed with unmanaged forests in terms of their contribution to climate change mitigation based on published data. For sustainably managed forests, accounting of carbon (C) storage based on ecosystem biomass and products as required by the United Nations Framework Convention on Climate Change is not sufficient to quantify their contribution to climate change mitigation. The ultimate value of biomass is its use for biomaterials and bioenergy. Taking Germany as an example, we show that the average removals of wood from managed forests are higher than stated by official reports, ranging between 56 and 86 mill. m³ year^?1 due to the unrecorded harvest of firewood. We find that removals from one hectare can substitute 0.87 m³ ha^?1 year^?1 of diesel, or 7.4 MWh ha^?1 year^?1, taking into account the unrecorded firewood, the use of fuel for harvesting and processing, and the efficiency of energy conversion. Energy substitution ranges between 1.9 and 2.2 t CO_{2 equiv.} ha^?1 year^?1 depending on the type of fossil fuel production. Including bioenergy and carbon storage, the total mitigation effect of managed forest ranges between 3.2 and 3.5 t CO_{2 equiv.} ha^?1 year^?1. This is more than previously reported because of the full accounting of bioenergy. Unmanaged nature conservation forests contribute via C storage only about 0.37 t CO_{2 equiv.}  ha^?1 year^?1 to climate change mitigation. There is no fossil fuel substitution. Therefore, taking forests out of management reduces climate change mitigation benefits substantially. There should be a mitigation cost for taking forest out of management in Central Europe. Since the energy sector is rewarded for the climate benefits of bioenergy, and not the forest sector, we propose that a CO₂ tax is used to award the contribution of forest management to fossil fuel substitution and climate change mitigation. This would stimulate the production of wood for products and energy substitution.     

Does High Cardiorespiratory Fitness Confer Some Protection Against Proinflammatory Responses After Infection by SARS‐CoV‐2?

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symptoms of SARS‐CoV‐2 and the subsequent prognosis are worsened in individuals who have preexisting comorbidities prior to infection by the virus. Individuals with obesity or overweight, insulin resistance, and diabetes typically have chronic low‐grade inflammation characterized by increased levels of several proinflammatory cytokines and the inflammasome; this state predisposes to greater risk for infection along with more adverse outcomes. Here, we consider whether a high level of cardiorespiratory fitness induced by prior exercise training may confer some innate immune protection against COVID‐19 by attenuating the “cytokine storm syndrome” often experienced by “at risk” individuals.     

Evolution of enzymes involved in the photorespiratory 2-phosphoglycolate cycle from cyanobacteria via algae toward plants

The photorespiratory pathway was shown to be essential for organisms performing oxygenic photosynthesis, cyanobacteria, algae, and plants, in the present day O(2)-containing atmosphere. The identification of a plant-like 2-phosphoglycolate cycle in cyanobacteria indicated that not only genes of oxygenic photosynthesis but also genes encoding photorespiratory enzymes were endosymbiotically conveyed from ancient cyanobacteria to eukaryotic oxygenic phototrophs. Here, we investigated the origin of the photorespiratory pathway in photosynthetic eukaryotes by phylogenetic analysis. We found that a mixture of photorespiratory enzymes of either cyanobacterial or α-proteobacterial origin is present in algae and higher plants. Three enzymes in eukaryotic phototrophs clustered closely with cyanobacterial homologs: glycolate oxidase, glycerate kinase, and hydroxypyruvate reductase. On the other hand, the mitochondrial enzymes of the photorespiratory cycle in algae and plants, glycine decarboxylase subunits and serine hydroxymethyltransferase, evolved from proteobacteria. Other than most genes for proteins of the photosynthetic machinery, nearly all enzymes involved in the 2-phosphogylcolate metabolism coexist in the genomes of cyanobacteria and heterotrophic bacteria.     

Fine-scale phosphorus distribution in coral skeletons: combining X-ray mapping by electronprobe microanalysis and LA-ICP-MS

Increased terrestrial phosphorus runoff is a major environmental problem that has been linked to deteriorating reef health. Unfortunately, long-term records of phosphorus are limited. Whilst phosphorus captured in coral skeletons could provide us with an archive of phosphorus variability, the mode of incorporation is poorly understood. In order to document phosphorus levels, we used laser ablation inductively coupled plasma mass spectrometry, followed by X-ray mapping of phosphorus in the skeleton at micron scale (~3–5 microns) using Electronprobe microanalysis. We recorded high phosphorus (≤8,700 ppm) in the living tissue zone associated with phosphorus-rich residues lining the internal pore network surfaces. The skeleton in the tissue zone had low, uniform levels of phosphorus, similar to older sections of the core (<50 ppm). Below the organic tissue layer, P was incorporated homogenously in the skeleton for extended periods (e.g., 5 mm growth bands). However, sections of the core (~1 cm down-core) displayed fine-scale elevated phosphorus concentrations associated with the presence of phosphorus-rich, often elongate (10–100 μm long), heterogeneities within the skeleton, the origin of these phosphorus-rich heterogeneities and their mode of incorporation requires further attention. In conclusion, these results support the continued development of this promising potential nutrient proxy.