载氢-纳米氧化铈微泡对小鼠造血系统抗辐射作用的分析

为探讨载氢-纳米氧化铈微泡对小鼠辐射损伤的防护作用。本研究检测载氢-纳米氧化铈微泡的表征,并将60只BALB/c小鼠随机分为正常对照组、照射对照组、载氢-纳米氧化铈微泡组。小鼠经6Gy x射线一次性全身照射(剂量率2 Gy/min)。于照射后3 d和8 d处死小鼠,检测其外周血细胞数、脾脏和胸腺指数、骨髓和脾脏组织病理学变化。结果显示,照射后3 d和8 d,与正常对照组相比,载氢-纳米氧化铈微泡组和照射对照组的白细胞均明显下降,相比照射对照组,载氢-纳米氧化铈微泡组有改善(p<0.05或p<0.01);而载氢-纳米氧化铈微泡组和照射对照组的红细胞数和血红蛋白均略有下降,但差异无统计学意义。与正常对照组相比,微泡组的胸腺指数、脾脏指数均有下降,和照射对照组相比,载氢-纳米氧化铈微泡组的胸腺指数明显改善(p<0.05或p<0.01)。照射后3 d,与正常对照组相比,照射对照组的骨髓细胞较少,存在细胞碎片,载氢-纳米氧化铈微泡组骨髓细胞数量略有减少,存在细胞核松散现象。而照射后8 d,与正常对照组相比,照射对照组的骨髓细胞几乎找不到,载氢-纳米氧化铈微泡组骨髓细胞有一定数量,存在细胞凋亡现象。本研究表明,载氢-纳米氧化铈微泡通过保护造血组织、改善造血功能,对机体起到一定的辐射防护作用。     

Raman–deuterium isotope probing to study metabolic activities of single bacterial cells in human intestinal microbiota

Human intestinal microbiota is important to host health and is associated with various diseases. It is a challenge to identify the functions and metabolic activity of microorganisms at the single-cell level in gut microbial community. In this study, we applied Raman microspectroscopy and deuterium isotope probing (Raman–DIP) to quantitatively measure the metabolic activities of intestinal bacteria from two individuals and analysed lipids and phenylalanine metabolic pathways of functional microorganisms in situ. After anaerobically incubating the human faeces with heavy water (D₂O), D₂O with specific substrates (glucose, tyrosine, tryptophan and oleic acid) and deuterated glucose, the C–D band in single-cell Raman spectra appeared in some bacteria in faeces, due to the Raman shift from the C–H band. Such Raman shift was used to indicate the general metabolic activity and the activities in response to the specific substrates. In the two individuals' intestinal microbiota, the structures of the microbial communities were different and the general metabolic activities were 76 ± 1.0% and 30 ± 2.0%. We found that glucose, but not tyrosine, tryptophan and oleic acid, significantly stimulated metabolic activity of the intestinal bacteria. We also demonstrated that the bacteria within microbiota preferably used glucose to synthesize fatty acids in faeces environment, whilst they used glucose to synthesize phenylalanine in laboratory growth environment (e.g. LB medium). Our work provides a useful approach for investigating the metabolic activity in situ and revealing different pathways of human intestinal microbiota at the single-cell level.     

The ROK-family regulator Rok7B7 directly controls carbon catabolite repression,antibiotic biosynthesis,and morphological development in Streptomyces avermitilis

Carbon catabolite repression (CCR) is a common phenomenon in bacteria that modulates expression of genes involved in uptake of alternative carbon sources. In the filamentous streptomycetes, which produce half of all known antibiotics, the precise mechanism of CCR is yet unknown. We report here that the ROK-family regulator Rok7B7 pleiotropically controls xylose and glucose uptake, CCR, development, as well as production of the macrolide antibiotics avermectin and oligomycin A in Streptomyces avermitilis. Rok7B7 directly repressed structural genes for avermectin biosynthesis, whereas it activated olmRI, the cluster-situated activator gene for oligomycin A biosynthesis. Rok7B7 also directly repressed the xylose uptake operon xylFGH, whose expression was induced by xylose and repressed by glucose. Both xylose and glucose served as Rok7B7 ligands. rok7B7 deletion led to enhancement and reduction of avermectin and oligomycin A production, respectively, relieved CCR of xylFGH, and increased co-uptake efficiency of xylose and glucose. A consensus Rok7B7-binding site, 5′-TTKAMKHSTTSAV-3′, was identified within aveA1p, olmRIp, and xylFp, which allowed prediction of the Rok7B7 regulon and confirmation of 11 additional targets involved in development, secondary metabolism, glucose uptake, and primary metabolic processes. Our findings will facilitate methods for strain improvement, antibiotic overproduction, and co-uptake of xylose and glucose in Streptomyces species.     

Three proline rotamases involved in calcium homeostasis play differential roles in stress tolerance,virulence and calcineurin regulation of Beauveria bassiana

FK506‐sensitive proline rotamases (FPRs), also known as FK506‐binding proteins (FKBPs), can mediate immunosuppressive drug resistance in budding yeast but their physiological roles in filamentous fungi remain opaque. Here, we report that three FPRs (cytosolic/nuclear 12.15‐kD Fpr1, membrane‐associated 14.78‐kD Fpr2 and nuclear 50.43‐kD Fpr3) are all equally essential for cellular Ca²⁺ homeostasis and contribute significantly to calcineurin activity at different levels in the insect‐pathogenic fungus Beauveria bassiana although the deletion of fpr1 alone conferred resistance to FK506. Radial growth, conidiation, conidial viability and virulence were less compromised in the absence of fpr1 or fpr2 than in the absence of fpr3, which abolished almost all growth on scant media and reduced growth moderately on rich media. The Δfpr3 mutant was more sensitive to Na⁺, K⁺, Mn²⁺, Ca²⁺, Cu²⁺, metal chelate, heat shock and UVB irradiation than was Δfpr2 while both mutants were equally sensitive to Zn²⁺, Mg²⁺, Fe²⁺, H₂O₂ and cell wall‐perturbing agents. In contrast, the Δfpr1 mutant was less sensitive to fewer stress cues. Most of 32 examined genes involved in DNA damage repair, Na⁺/K⁺ detoxification or osmotolerance and Ca²⁺ homeostasis were downregulated sharply in Δfpr2 and Δfpr3 but rarely so affected in Δfpr1, coinciding well with their phenotypic changes. These findings uncover important, but differential, roles of three FPRs in the fungal adaptation to insect host and environment and provide novel insight into their essential roles in calcium signalling pathway.     

NbALY916 is involved in potato virus X P25-triggered cell death in Nicotiana benthamiana

Systemic necrosis often occurs during viral infection of plants and is thought mainly to be the result of long-term stress induced by viral infection. Potato virus X (PVX) encodes the P25 pathogenicity factor that triggers a necrotic reaction during PVX-potato virus Ysynergistic coinfection. In this study, we discovered that NbALY916, a multifunctional nuclear protein, could interact with P25. When NbALY916 expression was reduced by tobacco rattle virus (TRV)-based virus-induced gene silencing, the accumulation of P25 was increased, which would be expected to cause more severe necrosis. However, silencing of NbALY916 reduced the extent of cell death caused by P25. Furthermore, we found that overexpression of NbALY916 increased the accumulation of H₂O₂ and triggered more extensive cell death when coexpressed with P25, even though accumulation of P25 was itself reduced by the increased expression of NbALY916. Furthermore, transient expression of P25 specifically induced the expression of NbALY916 mRNA, but not the mRNAs of three other ALYs in Nicotiana benthamiana. In addition, we showed that silencing of NbALY916 or transient overexpression of NbALY916 affected the infection of PVX in N. benthamiana. Our results reveal that NbALY916 has an antiviral role that, in the case of PVX, operates by inducing the accumulation of H₂O₂ and mediating the degradation of P25.     

Functional analyses of small secreted cysteine-rich proteins identified candidate effectors in Verticillium dahliae

Secreted small cysteine-rich proteins (SCPs) play a critical role in modulating host immunity in plant–pathogen interactions. Bioinformatic analyses showed that the fungal pathogen Verticillium dahliae encodes more than 100 VdSCPs, but their roles in host–pathogen interactions have not been fully characterized. Transient expression of 123 VdSCP-encoding genes in Nicotiana benthamiana identified three candidate genes involved in host–pathogen interactions. The expression of these three proteins, VdSCP27, VdSCP113, and VdSCP126, in N. benthamiana resulted in cell death accompanied by a reactive oxygen species burst, callose deposition, and induction of defence genes. The three VdSCPs mainly localized to the periphery of the cell. BAK1 and SOBIR1 (associated with receptor-like protein) were required for the immunity triggered by these three VdSCPs in N. benthamiana. Site-directed mutagenesis showed that cysteine residues that form disulphide bonds are essential for the functioning of VdSCP126, but not VdSCP27 and VdSCP113. VdSCP27, VdSCP113, and VdSCP126 individually are not essential for V. dahliae infection of N. benthamiana and Gossypium hirsutum, although there was a significant reduction of virulence on N. benthamiana and G. hirsutum when inoculated with the VdSCP27/VdSCP126 double deletion strain. These results illustrate that the SCPs play a critical role in the V. dahliae–plant interaction via an intrinsic virulence function and suppress immunity following infection.     

Prioritising African perspectives in psychiatric genomics research: Issues of translation and informed consent

Psychiatric genomics research with African populations comes with a range of practical challenges around translation of psychiatric genomics research concepts, procedures, and nosology. These challenges raise deep ethical issues particularly around legitimacy of informed consent, a core foundation of research ethics. Through a consideration of the constitutive function of language, the paper problematises like‐for‐like, designative translations which often involve the ‘indigenization’ of English terms or use of metaphors which misrepresent the risks and benefits of research. This paper argues that effective translation of psychiatric genomics research terminology in African contexts demands substantive engagement with African conceptual schemas and values. In developing attenuated forms of translational thinking, researchers may recognise the deeper motivational reasons behind participation in research, highlighting the possibility that such reasons may depart from the original meaning implied within informed consent forms. These translational issues might be ameliorated with a critical re‐examination of how researchers develop and present protocols to institutional ethics review boards.     

CHIP modulates APP‐induced autophagy‐dependent pathological symptoms in Drosophila

Dysregulation of autophagy is associated with the neurodegenerative processes in Alzheimer's disease (AD), yet it remains controversial whether autophagy is a cause or consequence of AD. We have previously expressed the full‐length human APP in Drosophila and established a fly AD model that exhibits multiple AD‐like symptoms. Here we report that depletion of CHIP effectively palliated APP‐induced pathological symptoms, including morphological, behavioral, and cognitive defects. Mechanistically, CHIP is required for APP‐induced autophagy dysfunction, which promotes Aβ production via increased expression of BACE and Psn. Our findings suggest that aberrant autophagy is not only a consequence of abnormal APP activity, but also contributes to dysregulated APP metabolism and subsequent AD pathogenesis.