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Background: Accumulating evidence indicates that RNA oxidation is involved in a wide variety of neurological diseases and may be associated with neuronal deterioration during the process of neurodegeneration. However, previous studies were done in postmortem tissues or cultured neurons. Here, we used transgenic mice to demonstrate the role of RNA oxidation in the process of neurodegeneration. Methodology/Principal Findings: We demonstrated that messenger RNA (mRNA) oxidation is a common feature in amyotrophic lateral sclerosis (ALS) patients as well as in many different transgenic mice expressing familial ALS-linked mutant copper-zinc superoxide dismutase (SOD1). In mutant SOD1 mice, increased mRNA oxidation primarily occurs in the motor neurons and oligodendrocytes of the spinal cord at an early, pre-symptomatic stage. Identification of oxidized mRNA species revealed that some species are more vulnerable to oxidative damage, and importantly, many oxidized mRNA species have been implicated in the pathogenesis of ALS. Oxidative modification of mRNA causes reduced protein expression. Reduced mRNA oxidation by vitamin E restores protein expression and partially protects motor neurons. Conclusion/Significance: These findings suggest that mRNA oxidation is an early event associated with motor neuron deterioration in ALS, and may be also a common early event preceding neuron degeneration in other neurological diseases. [ABSTRACT FROM AUTHOR]

Transgenic mice expressing mutant Cu2+/ Zn2+ superoxide dismutase SOD1(G93A) develop similar clinical and pathological phenotypes to amyotrophic lateral sclerosis (ALS) patients. Here, we utilize representational difference analysis to identify the transcripts that are up-regulated in the presymptomatic stage of SOD1(G93A) mice. Unexpectedly, three predominant clones were 18S or 28S ribosomal RNA (rRNA) segments. One of these clones corresponded to a capped and polyadenylated transcript containing a largeportion of 18S rRNA, named MSUR1 (mutant SOD1-up-regulated RNA 1). In vitro expression experiments show that MSUR1 is able to rescue SOD1(G93A)-mediated cell death. Expression of MSUR1 significantly reduces SOD1 (G93A)-induced free radical levels and oxidative damage. Further, MSUR1 can reduce hydrogen peroxide-mediated cytotoxicity. MSUR1 does not encode a protein, suggesting its role as a functional noncoding RNA. It is widely expressed in various tissues. Searching the database of GenBank revealed that a large number of expressed sequence tag (EST) clones contain large portions of rRNA sequence, potentially indicating a heretofore overlooked class of mRNAs with functional significance. [ABSTRACT FROM AUTHOR]

We previously reported that up to 50% of messenger RNAs (mRNA) are oxidatively damaged in the affected area of Alzheimer's disease (AD) brains. The role of RNA oxidation in the cell death process is unknown. In the present study, we used cortical primary dissociated cultures to investigate the relationship between RNA oxidation and neuron degeneration induced by various insults, including hydrogen peroxide, glutamate, and amyloid β peptide. These insults mediate the production of reactive oxygen species and thus induce oxidative stress. The results showed that RNA oxidation was an early event far preceding cell death, not merely a consequence of dying cells. RNA oxidation occurred primarily in a distinct group of neurons that died later. Identification of oxidized RNA species revealed that significant amounts of mRNAs were oxidized and that some mRNA species were more susceptible to oxidative damage, consistent with findings in the AD brain. The level of protein corresponding to the oxidized mRNA species was significantly decreased. Polyribosome analysis indicated that oxidized bases in mRNAs caused ribosome stalling on the transcripts, which led to a decrease of protein expression. These results suggest that RNA oxidation may be directly associated with neuronal deterioration, rather than harmless epiphenomenona, during the process of neurodegeneration. [ABSTRACT FROM AUTHOR]

Radar remote sensing can acquire information of sub-surface covered by sand in arid area, detect surface roughness and vegetation coronet’s layer and linear feature such as linear structure and channel sensitively. With sediment facies analysis, this paper studies the features of environmental evolution in mid-late Epipleistocene (60 ka BP-20 ka BP) in northeastern Ejin Banner. The conclusions are listed as follows: (1) The evolution of the three lakes, i.e. Gaxunnur, Sugunur and Tian’e lakes, are dominated by faults and regional climate. (2) By analyzing sedimentary section of old Juyanze Lake, the three lakes used to be a large outflow lake before 50 ka BP in northeastern Ejin Banner, and at 50 ka BP, temperature declined rapidly in northwestern China. The event caused the lake’s shrinkage. (3) By fault activity uplift in the northern part of old Juyan Lake and depression in the southern part, the lake’s water followed from north to south at around 35 ka BP, old Juyanze fluvial fan was formed. At the same time, Juyan Lake separated from Sugunur Lake and Wentugunr old channel was abandoned. (4) In recent 2000 years, Ruoshui River is a wandering river, sometimes it flows into Juyan Lake and sometimes Sugunur and Gaxunnur lakes. Due to human activities and over exploitation, the oasis ecosystem is rapidly degenerated in 15 years (1986–2000). [ABSTRACT FROM AUTHOR]