Intra- and intercellular RNA interference in Arabidopsis thaliana requires components of the microRNA and heterochromatic silencing pathways

In RNA interference (RNAi), double-stranded RNA (dsRNA) is processed into short interfering RNA (siRNA) to mediate sequence-specific gene knockdown. The genetics of plant RNAi is not understood, nor are the bases for its spreading between cells. Here, we unravel the requirements for biogenesis and action of siRNAs directing RNAi in Arabidopsis thaliana and show how alternative routes redundantly mediate this process under extreme dsRNA dosages. We found that SMD1 and SMD2, required for intercellular but not intracellular RNAi, are allelic to RDR2 and NRPD1a, respectively, previously implicated in siRNA-directed heterochromatin formation through the action of DCL3 and AGO4. However, neither DCL3 nor AGO4 is required for non-cell autonomous RNAi, uncovering a new pathway for RNAi spreading or detection in recipient cells. Finally, we show that the genetics of RNAi is distinct from that of antiviral silencing and propose that this experimental silencing pathway has a direct endogenous plant counterpart.     

长白山地区幔源捕虏体的硫化物相及其演化

长白山地区新生代玄武岩的一些层位广布地幔岩捕虏体,在其橄榄石、辉石等矿物内发现有较多的硫化物相,按产出特征可鉴别出3种类型,即早期硫化物颗粒、硫化物包裹体和裂隙中硫化物。硫化物包裹体可以单相硫化物、硫化物－硅酸盐熔体、CO2－硫化物－硅酸盐熔体形式存在。早期硫化物颗粒以磁黄铁矿为主,并发现有方黄铜矿;硫化物包裹体以镍黄铁矿为主,并有黄铜矿、硫铜铁矿出现;裂隙中硫化物均为镍黄铁矿,并具有比硫化物包裹体高的Ni/Fe和（Fe Ni)／S值。地幔岩中存在自早期硫化物颗粒、硫化物包裹体至裂隙硫化物,Ni/Fe和（Fe Ni)/S比值逐渐增加的规律。这种演化不仅受温度和压力制约,而且受Ni,Fe,Cu的地球化学特性和硫逸度的控制。     

Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production

Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson’s disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons. A time- and dose-dependent accumulation of α-syn was observed following PFFs exposure that also underwent phosphorylation at serine 129. PFFs treatment decreased the expression levels of synaptic proteins, caused alterations in axonal transport-related proteins, and increased H2AX Ser139 phosphorylation. Mitochondrial impairment (including modulation of mitochondrial dynamics-associated protein content), enhanced oxidative stress, and an inflammatory response were also detected in our experimental paradigm. In attempt to unravel a potential molecular mechanism of PFFs neurotoxicity, the expression of inducible nitric oxide synthase was blocked; a significant decline in protein nitration levels and protection against PFFs-induced DA neuron death were observed. Combined exposure to PFFs and rotenone resulted in an additive toxicity. Strikingly, many of the harmful effects found were more prominent in DA rather than non-DA neurons, suggestive of higher susceptibility to degenerate. These findings provide new insights into the role of α-syn in the pathogenesis of PD and could represent a novel and valuable model to study DA-related neurodegeneration.