Histone deacetylase 6 interacts with the microtubule-associated protein tau

Histone deacetylase 6 (HDAC6), a unique cytoplasmic deacetylase, likely plays a role in neurodegeneration by coordinating cell responses to abnormal protein aggregation. Here, we provide in vitro and in vivo evidence that HDAC6 interacts with tau, a microtubule-associated protein that forms neurofibrillary tangles in Alzheimer's disease. This interaction is mediated by the microtubule-binding domain on tau and the Ser/Glu tetradecapeptide domain on HDAC6. Treatment with tubacin, a selective inhibitor of tubulin deacetylation activity of HDAC6, did not disrupt HDAC6–tau interaction. Nonetheless tubacin treatment attenuated site-specific tau phosphorylation, as did shRNA-mediated knockdown of HDAC6. Proteasome inhibition potentiated HDAC6–tau interactions and facilitated the concentration and co-localization of HDAC6 and tau in a perinuclear aggresome-like compartment, independent of HDAC6 tubulin deacetylase activity. Furthermore, we observed that in Alzheimer's disease brains the protein level of HDAC6 was significantly increased. These findings establish HDAC6 as a tau-interacting protein and as a potential modulator of tau phosphorylation and accumulation.     

T cell responses to whole SARS coronavirus in humans

Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.     

Novel Design Concepts of Efficient Mg‐Ion Electrolytes toward High‐Performance Magnesium–Selenium and Magnesium–Sulfur Batteries

Developing high‐voltage Mg‐compatible electrolytes (>3.0 V vs Mg) still remains to be the biggest R&D challenge in the area of nonaqueous rechargeable Mg batteries. Here, the key design concepts toward exploring new boron‐based Mg salts in a specific way of highlighting the implications of anions are proposed for the first time. The well‐defined boron‐centered anion‐based magnesium electrolyte (BCM electrolyte) is successfully presented by facile one‐step mixing of tris(2H‐hexafluoroisopropyl) borate and MgF₂ in 1,2‐dimethoxyethane, in which the structures of anions have been thoroughly investigated via mass spectrometry accompanied by NMR and Raman spectra. The first all‐round practical BCM electrolyte fulfills all requirements of easy synthesis, high ionic conductivity, wide potential window (3.5 V vs Mg), compatibility with electrophilic sulfur, and simultaneously noncorrosivity to coin cell assemblies. When utilizing the BCM electrolyte, the fast‐kinetics selenium/carbon (Se/C) cathode achieves the best rate capability and the sulfur/carbon (S/C) cathode exhibits an impressive prolonged cycle life than previously published reports. The BCM electrolyte offers the most promising avenue to eliminate the major roadblocks on the way to high‐voltage Mg batteries and the design concepts can shed light on future exploration directions toward high‐voltage Mg‐compatible electrolytes.     

CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

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Molecular cloning and characterization of <Emphasis Type="Italic">S</Emphasis>-adenosylmethionine decarboxylase gene in rubber tree (<Emphasis Type="Italic">Hevea brasiliensis</Emphasis>)

S-Adenosylmethionine decarboxylase (SAMDC) is a key rate-limiting enzyme involved in polyamines biosynthesis, and it plays important roles in plant growth, development and stresses response. However, no SAMDC gene was reported in rubber tree. Here we report characteristics of an SAMDC gene (HbSAMDC1) in rubber tree. HbSAMDC1 contains a 1080 bp open reading frame (ORF) encoding 359 amino acids. Quantitative real-time PCR analyses revealed that HbSAMDC1 exhibited distinct expression patterns in different tissues and was regulated by various stresses, including drought, cold, salt, wounding, and H₂O₂ treatments. HbSAMDC1 5′ untranslated region (UTR) contains a highly conserved overlapping tiny and small upstream ORFs (uORFs), encoding 2 and 52 amino acid residues, respectively. No introns were located in the main ORF of HbSAMDC1, whereas two introns were found in the 5′ UTR. In transgenic tobaccos, the highly conserved small uORF of HbSAMDC1 is found to be responsible for translational repression of downstream β-glucuronidase reporter. To our knowledge, this is the first report on molecular cloning, expression profiles, and 5′ UTR characteristics of HbSAMDC1. These results lay solid foundation for further elucidating HbSAMDC1 function in rubber tree.     

沼肥与化肥在大白菜、花椰菜上的应用效果比较研究

以大白菜、花椰菜为试材 ,研究了沼肥、化肥两种肥料在高量、中量、低量 3个施用水平下的施用效果。结果表明 ,从株高指标上看 ,大白菜施沼肥以低量为佳 ,花椰菜以高量为好 ;从开展度指标上看 ,大白菜、花椰菜施沼肥均以低量为好 ;从单球净重上看 ,两种蔬菜均以施沼肥中量利于提高单球净重 ;从提高净菜率来看 ,大白菜以沼肥中量处理为好 ,花椰菜以沼肥高量处理为佳 ;从两种蔬菜的产量来看 ,施沼肥处理均显著高于施化肥处理 ,其中沼肥高量与沼肥中量处理之间无显著差异 ,而它们与沼肥低量处理之间存在显著差异 ;大白菜中的总糖含量以沼肥低量处理为最高 ,而花椰菜则以沼肥中量处理最高 ;两种蔬菜中的Vc含量均以化肥高量处理为最高 ;从两种蔬菜收获时霜霉病的发病情况来看 ,均以沼肥中量处理发病最轻。施用沼肥利于改善土壤理化性状 ,利于大白菜、花椰菜对土壤中营养元素的吸收 ,从而致使土壤中营养元素的积累量减少。     

温湿度对安徽虫瘟霉在桃蚜居群中流行的影响

用安徽虫瘟霉(Zoopphthoraanhuiensis)接种桃蚜(Myzuspersicae)无翅成蚜3头和健蚜3头组成新的蚜群若干,在不同温湿组合条件下任其繁殖、发病和传染,以评价温湿度对该菌在蚜群中流行的影响.持续26d观察,在偏低温与各湿度(90～100%RH)的组合中均成功诱发了蚜病流行,其程度受湿度影响较小.在10℃与各湿度组合中,最终感病死亡率为72.9%～98.2%,15℃下为78.7%～94.4%,流行强度极大.而20℃下仅100%RH诱发了高强度流行病,其余湿度下感病死亡率仅为5.1%～12.8%.在25℃,100%RH下死亡率仅27.2%.与所有湿度组合中的对照蚜群相比,10℃下流行病控蚜效果为89.5%～96.9%,15℃下为96.1%～98.2%,20℃下为45.9%～85.7%,25℃下为56.4%～69.7%.逐步回归分析表明,安徽虫瘟霉引发的蚜病流行与温度及其相对湿度和蚜群带菌后天数的互作项密切相关(r2=0.82,a＜0.01),这些变量在很大程度上决定了安徽虫瘟霉是否在蚜群中流行.     

Correction to: TREM2 Attenuates Aβ1-42-Mediated Neuroinflammation in BV-2 Cells by Downregulating TLR Signaling

Neurochemical Research - The article titled “TREM2 Attenuates Aβ1?42?Mediated Neuroinflammation in BV?2 Cells by Downregulating TLR Signaling”, written by Huiping...     

Retracted: GABARAP promotes bone marrow mesenchymal stem cells-based the osteoarthritis cartilage regeneration through the inhibition of PI3K/AKT/mTOR signaling pathway

Osteoarthritis (OA) is a degenerative disease of the cartilage prevalent in the middle-aged and elderly demographic. Direct transplantation of bone marrow mesenchymal stem cells (BMSCs) or stem cell-derived chondrocytes into the damaged cartilage is a promising therapeutic strategy for OA, but is limited by the poor survival and in situ stability of the chondrocytes. Autophagy is a unique catabolic pathway conserved across eukaryotes that maintains cellular homeostasis, recycles damaged proteins and organelles, and promotes survival. The aim of this study was to determine the role of the proautophagic γ-aminobutyric acid receptor-associated protein (GABARAP) on the therapeutic effects of BMSCs-derived chondrocytes in a rat model of OA, and elucidate the underlying mechanisms. Anterior cruciate ligament transection (ACLT) was performed in Sprague–Dawley rats to simulate OA, and the animals were injected weekly with recombinant human His6-GABARAP protein, BMSCs-derived differentiated chondrocytes (DCs) or their combination directly into the knee cartilage. The regenerative effects of GABARAP and/or DCs were determined in term of International Cartilage Repair Society scores and cartilage thickness. The combination treatment of DCs and GABARAP significantly increased the levels of the ECM proteins Col II and SOX9, indicating formation of hyaline-like cartilage, and decreased chondrocyte apoptosis and inflammation. DCs + GABARAP treatment also upregulated the mediators of the autophagy pathway and suppressed the PI3K/AKT/mTOR pathway, indicating a mechanistic basis of its therapeutic action.