Significance of HLA class I antibody-induced antioxidant gene expression for endothelial cell protection against complement attack

It has been observed that a graft organ continues to survive and function normally even in the presence of anti-graft antibodies. However, the mechanisms behind acquirement of this condition remain unknown. Here we report that the anti-HLA ligation on endothelial cells induces PI3K/AKT activation followed by antioxidant gene induction through Nrf2-mediated antioxidant-responsive element (ARE) activation. Activation of PI3K/AKT in endothelial cells by a low concentration of anti-HLA ligation enhances protection from complement attack. A real-time quantitative PCR and flow-cytometry experiment showed that ferritin H and HO-1 mRNAs were induced in a PI3K/AKT-dependent manner, while CD55 and CD59 expression were not enhanced by anti-HLA ligation. Anti-HLA ligation on endothelial cells activates ferritin H ARE and induces Nrf2 binding on its enhancer element. Finally, overexpression of Nrf2 in endothelial cells attenuates complement-mediated cytotoxicity. These experiments suggest that induction of PI3K/AKT-dependent cytoprotective genes by Nrf2 is an important mechanism to prevent complement attack. Thus, a protocol to activate this pathway would be a potential strategy for avoidance of graft rejection in transplantation.     

DNA barcodes reveal species-specific mercury levels in tuna sushi that pose a health risk to consumers

Excessive ingestion of mercury—a health hazard associated with consuming predatory fishes—damages neurological, sensory-motor and cardiovascular functioning. The mercury levels found in Bigeye Tuna (Thunnus obesus) and bluefin tuna species (Thunnus maccoyii, Thunnus orientalis, and Thunnus thynnus), exceed or approach levels permissible by Canada, the European Union, Japan, the US, and the World Health Organization. We used DNA barcodes to identify tuna sushi samples analysed for mercury and demonstrate that the ability to identify cryptic samples in the market place allows regulatory agencies to more accurately measure the risk faced by fish consumers and enact policies that better safeguard their health.     

血清GPAA1、SF、OPN与儿童急性淋巴细胞白血病危险度的关系及对血栓发生风险的评估效能研究

摘要 目的：分析血清糖基磷脂酰肌醇锚附着蛋白1（GPAA1）、铁蛋白（SF）、骨桥蛋白（OPN）与儿童急性淋巴细胞白血病危险度的关系及对血栓发生风险的评估效能。方法：选择我院自2017年1月至2022年12月接诊的112例急性淋巴细胞白血病患儿作为观察组，另选112例性别、年龄与观察组相匹配的健康体检儿童作为对照组。检测两组血清GPAA1、SF、OPN表达水平，分析不同危险度的急性淋巴细胞白血病患儿血清GPAA1、SF、OPN表达水平的差异性，观察急性淋巴细胞白血病患儿的血栓发生情况，通过受试者工作特征曲线（ROC）下面积（AUC）评价血清GPAA1、SF、OPN预测急性淋巴细胞白血病患儿发生血栓的效能。结果：观察组血清GPAA1、SF、OPN表达水平均高于对照组（P＜0.05）；在低危、中危和高危的急性淋巴细胞白血病患儿中，血清GPAA1、SF、OPN表达水平有差异（P＜0.05）；经Spearman相关性分析，血清GPAA1、SF、OPN表达水平与儿童急性淋巴细胞白血病危险度呈正相关（P＜0.05）；在112例急性淋巴细胞白血病患儿中，发生血栓12例，占10.71%；经多因素Logistic回归分析，血清GPAA1、SF、OPN均是急性淋巴细胞白血病患儿发生血栓的独立预测因素（P＜0.05）；经ROC曲线分析，血清GPAA1、SF联合OPN预测急性淋巴细胞白血病患儿发生血栓的AUC为0.901。结论：血清GPAA1、SF、OPN与儿童急性淋巴细胞白血病危险度密切相关，联合预测患儿发生血栓的效能较好，对此病的诊治具有重要指导意义。     

The chemical form of mitochondrial iron in Friedreich's ataxia

Friedreich's ataxia (FRDA) results from cellular damage caused by a deficiency in the mitochondrial matrix protein frataxin. To address the effect of frataxin deficiency on mitochondrial iron chemistry, the heavy mitochondrial fraction (HMF) was isolated from primary fibroblasts from FRDA affected and unaffected individuals. X-ray absorption spectroscopy was used to characterize the chemical form of iron. Near K-edge spectra were fitted with a series of model iron compounds to determine the proportion of each iron species. Most of the iron in both affected and unaffected fibroblasts was ferrihydrite. The iron K-edge from unaffected HMFs were best fitted with poorly organized ferrihydrite modeled by frataxin whereas HMFs from affected cells were best fitted with highly organized ferrihydrite modeled by ferritin. Both had several minor iron species but these did not differ consistently with disease. Since the iron K-edge spectra of ferritin and frataxin are very similar, we present additional evidence for the presence of ferritin-bound iron in HMF. The predominant ferritin subunit in HMFs from affected cells resembled mitochondrial ferritin (MtFt) in size and antigenicity. Western blotting of native gels showed that HMF from affected cells had 3-fold more holoferritin containing stainable iron. We conclude that most of the iron in fibroblast HMF from both affected and unaffected cells is ferrihydrite but only FRDA affected cells mineralize significant iron in mitochondrial ferritin.     

Nitrogen resorption and photosynthetic activity over leaf life span in an evergreen shrub, Rhododendron ferrugineum, in a subalpine environment

Here, the advantages for a shrub of having long vs short-lived leaves was investigated in Rhododendron ferrugineum by following nitrogen(15N) and carbon(14C) resorption and translocation, and photosynthetic capacity over the life span. Mean leaf life span was 19 months. Nitrogen (N) resorption in attached leaves occurred mainly in the first year (23%) and reached a maximum of 31% in the second. Although, resorption was similar in attached and fallen 1-yr-old leaves, it was on average one-third higher in fallen than in attached older leaves. Final N resorption of a leaf compartment reached 41%, half occurring from healthy leaves during the first year. Photosynthetic capacity decreased slightly during the life span. Before shoot growth, plant photosynthesis was mainly supported by 1-yr-old leaves, although the contribution of the 2-yr-old leaves was nonnegligible (15% of the capacity and higher carbon transfer toward the roots). After shoot growth, the current-year leaves made the greatest contribution. Our results suggest that short-lived leaves (half of the cohort) are mainly involved in a photosynthetic function, having a high photosynthetic capacity and drawing most of their resorbed N towards current-year leaves; and long-lived leaves are also involved in a conservative function, increasing N resorption and mean residence time (MRT).     

Rhizodeposition shapes rhizosphere microbial community structure in organic soil

The aims of the study were to determine group specificity in microbial utilization of root-exudate compounds and whole rhizodeposition; quantify the proportions of carbon acquired by microbial groups from soil organic matter and rhizodeposition, respectively; and assess the importance of root-derived C as a driver of soil microbial community structure. Additions of 13C-labelled root-exudate compounds to organic soil and steady-state labelling of Lolium perenne, coupled to compound-specific isotope ratio mass spectrometry, were used to quantify group-specific microbial utilization of rhizodeposition. Microbial utilization of glucose and fumaric acid was widespread through the microbial community, but glycine was utilized by a narrower range of populations, as indicated by the enrichment of phospholipid fatty acid (PLFA) analysis fractions. In L. perenne rhizospheres, high rates of rhizodeposit utilization by microbial groups showed good correspondence with increased abundance of these groups in the rhizosphere. Although rhizodeposition was not the quantitatively dominant C source for microbes in L. perenne rhizospheres, relative utilization of this C source was an important driver of microbial group abundance in organic soil.     

Does carbon partitioning in ectomycorrhizal pine seedlings under elevated CO2 vary with fungal species?

Enhanced soil respiration in response to elevated atmospheric CO₂ has been demonstrated, and ectomycorrhizal (ECM) fungi are of particular interest since they partition host-derived photoassimilates belowground. Although a strong response of ECM fungi to elevated CO₂ has been shown, little is still known about the functional diversity among species. We studied carbon (C) partitioning in mycorrhizal Scots pine seedlings in response to short-term CO₂ enrichment, using seven ECM species with different ecological strategies. Mycorrhizal associations were synthesised and seedlings grown in large Petri dishes containing peat:vermiculite and nutrient solution for 10–15 weeks, after which half of the microcosms were exposed to elevated CO₂ treatment (710 ppm) for 15 days and the other half were kept in ambient CO₂ treatment. Partitioning of C was quantified by pulse labelling the seedlings with ¹⁴CO₂ and examining the distribution of labelled assimilates in shoot, root and extraradical mycelial compartments by destructive harvest and liquid scintillation counting. Fungal biomass was determined with PLFA analysis. The respiratory loss of ¹⁴CO₂ was on average greater in the elevated CO₂ treatment for most species compared to the ambient CO₂ treatment. More label was retrieved in the shoots in the ambient CO₂ treatment compared to elevated CO₂ (significant for P. involutus and P. fallax). Greater amounts of label were found in the extraradical mycelial compartment in all species (except P. involutus) in elevated CO₂ compared to ambient CO₂ (significant for L. bicolor, P. byssinum, P. fallax and R. roseolus). Fungal biomass production increased significantly with elevated CO₂ for two species (H. velutipes and A. muscaria); three species (P. fallax, P. involutus and R. roseolus) showed a similar but non-significant trend, whereas L. bicolor and P. byssinum produced less biomass in elevated CO₂ compared to ambient CO₂. When ¹⁴C in the mycelial compartment and respiration was expressed per unit fungal PLFA the difference between CO₂ treatments disappeared. We demonstrated that different ECM fungal isolates respond differently in C partitioning in response to CO₂ enrichment. These results suggest that under certain growth conditions, when nutrients are not limiting, ECM fungi respond rapidly to increasing C-availability through changed biomass production and respiration.     

Synthesis and analytics of 2,2,3,4,4-d5-19-nor-5alpha-androsterone--an internal standard in doping analysis

A short and efficient synthesis of pentadeuterated 2,2,3,4,4-d5-19-nor-5alpha-androsterone 7 starting from 19-norandrost-4-ene-3,17-dione 1 by a d1-L-Selectride mediated stereo- and regioselective reduction of the 3-keto group is presented. The use of compound 7 as internal standard for the detection of anabolic steroids via mass spectrometric techniques such as gas chromatography-mass spectrometry (GC-MS) is discussed.     

The Pivotal Role of Astrocytes in the Metabolism of Iron in the Brain

Iron is essential for the normal functioning of cells but since it is also capable of generating toxic reactive oxygen species, the metabolism of iron is tightly regulated. The present article advances the view that astrocytes are largely responsible for distributing iron in the brain. Capillary endothelial cells are separated from the neuropil by the endfeet of astrocytes, so astrocytes are ideally positioned to regulate the transport of iron to other brain cells and to protect them if iron breaches the blood-brain barrier. Astrocytes do not appear to have a high metabolic requirement for iron yet they possess transporters for transferrin, haemin and non-transferrin-bound iron. They store iron efficiently in ferritin and can export iron by a mechanism that involves ferroportin and ceruloplasmin. Since astrocytes are a common site of abnormal iron accumulation in ageing and neurodegenerative disorders, they may represent a new therapeutic target for the treatment of iron-mediated oxidative stress.     

Interactions between soil and tree roots accelerate long-term soil carbon decomposition

Decomposition of soil organic carbon (SOC) is the main process governing the release of CO₂ into the atmosphere from terrestrial systems. Although the importance of soil–root interactions for SOC decomposition has increasingly been recognized, their long-term effect on SOC decomposition remains poorly understood. Here we provide experimental evidence for a rhizosphere priming effect, in which interactions between soil and tree roots substantially accelerate SOC decomposition. In a 395-day greenhouse study with Ponderosa pine and Fremont cottonwood trees grown in three different soils, SOC decomposition in the planted treatments was significantly greater (up to 225%) than in soil incubations alone. This rhizosphere priming effect persisted throughout the experiment, until well after initial soil disturbance, and increased with a greater amount of root-derived SOC formed during the experiment. Loss of old SOC was greater than the formation of new C, suggesting that increased C inputs from roots could result in net soil C loss.