Manganese overexposure induces Parkinson-like symptoms, altered lipid signature and oxidative stress in C57BL/6 J mouse

Although adequate intake of manganese (Mn) is essential to humans, Mn in excess is neurotoxic. Exposure to extremely high doses of Mn results in “manganism”, a condition that exhibits Parkinson-like symptoms. However, the mechanisms underlying its neurotoxic effects in Mn-induced parkinsonism pathogenesis are unclear. In this study, 8-week-old male C57BL/6 J mice were injected intraperitoneally with saline and 50 mg/kg MnCl2 respectively once daily for 14 days to produce an acute Mn neurotoxicity model. Accumulation of Mn in the midbrain, motor dysfunction and loss of dopaminergic neurons in the substantia nigra evidenced Mn neurotoxicity. Untargeted lipidomic analysis demonstrated that Mn overexposure altered lipidome profiles. A significant modulation of 12 lipid subclasses belonging to 5 different categories were found in the midbrain and among the most abundant lipids were sphingolipids, glycerophospholipids, and glycerides. The levels of sphingomyelin (SM) were significantly decreased after Mn treatment. The expression of SM biosynthesis genes was decreased dramatically while sphingomyelinase was up-regulated. In addition, we observed oxidative stress in both the midbrain of mice and MN9D cells, indicated by the increase of MDA level, the decrease of reduced GSH level and the inhibition of SOD and GPx enzyme activities. There was a correlation between these changes and motor dysfunctions. Overall, our study is the first to use lipidomics techniques to explore the pathogenesis of Mn-induced parkinsonism in C57BL/6 J mice. Mn induced molecular events in the midbrain, such as lipid metabolism disorders, oxidative stress and dopaminergic neurons injury, may mechanistically play important roles in the pathogenesis of Parkinson-like symptoms. Moreover, these findings emphasize the necessity for reducing the health risk of environmental neurotoxic pollutants in relation to parkinsonism

High-throughput deep sequencing reveals that microRNAs play important roles in salt tolerance of euhalophyte Salicornia europaea

Background: microRNAs (miRNAs) are implicated in plant development processes and play pivotal roles in plant adaptation to environmental stresses. Salicornia europaea, a salt mash euhalophyte, is a suitable model plant to study salt adaptation mechanisms. S. europaea is also a vegetable, forage, and oilseed that can be used for saline land reclamation and biofuel precursor production on marginal lands. Despite its importance, no miRNA has been identified from S. europaea thus far. Results: Deep sequencing was performed to investigate small RNA transcriptome of S. europaea. Two hundred and ten conserved miRNAs comprising 51 families and 31 novel miRNAs (including seven miRNA star sequences) belonging to 30 families were identified. About half (13 out of 31) of the novel miRNAs were only detected in salt-treated samples. The expression of 43 conserved and 13 novel miRNAs significantly changed in response to salinity. In addition, 53 conserved and 13 novel miRNAs were differentially expressed between the shoots and roots. Furthermore, 306 and 195 S. europaea unigenes were predicted to be targets of 41 conserved and 29 novel miRNA families, respectively. These targets encoded a wide range of proteins, and genes involved in transcription regulation constituted the largest category. Four of these genes encoding laccase, F-box family protein, SAC3/GANP family protein, and NADPH cytochrome P-450 reductase were validated using 5'-RACE. Conclusions: Our results indicate that specific miRNAs are tightly regulated by salinity in the shoots and/or roots of S. europaea, which may play important roles in salt tolerance of this euhalophyte. The S. europaea salt-responsive miRNAs and miRNAs that target transcription factors, nucleotide binding site-leucine-rich repeat proteins and enzymes involved in lignin biosynthesis as well as carbon and nitrogen metabolism may be applied in genetic engineering of crops with high stress tolerance, and genetic modification of biofuel crops with high biomass and regulatable lignin biosynthesis

High-throughput deep sequencing reveals that microRNAs play important roles in salt tolerance of euhalophyte Salicornia europaea

Background: microRNAs (miRNAs) are implicated in plant development processes and play pivotal roles in plant adaptation to environmental stresses. Salicornia europaea, a salt mash euhalophyte, is a suitable model plant to study salt adaptation mechanisms. S. europaea is also a vegetable, forage, and oilseed that can be used for saline land reclamation and biofuel precursor production on marginal lands. Despite its importance, no miRNA has been identified from S. europaea thus far. Results: Deep sequencing was performed to investigate small RNA transcriptome of S. europaea. Two hundred and ten conserved miRNAs comprising 51 families and 31 novel miRNAs (including seven miRNA star sequences) belonging to 30 families were identified. About half (13 out of 31) of the novel miRNAs were only detected in salt-treated samples. The expression of 43 conserved and 13 novel miRNAs significantly changed in response to salinity. In addition, 53 conserved and 13 novel miRNAs were differentially expressed between the shoots and roots. Furthermore, 306 and 195 S. europaea unigenes were predicted to be targets of 41 conserved and 29 novel miRNA families, respectively. These targets encoded a wide range of proteins, and genes involved in transcription regulation constituted the largest category. Four of these genes encoding laccase, F-box family protein, SAC3/GANP family protein, and NADPH cytochrome P-450 reductase were validated using 5'-RACE. Conclusions: Our results indicate that specific miRNAs are tightly regulated by salinity in the shoots and/or roots of S. europaea, which may play important roles in salt tolerance of this euhalophyte. The S. europaea salt-responsive miRNAs and miRNAs that target transcription factors, nucleotide binding site-leucine-rich repeat proteins and enzymes involved in lignin biosynthesis as well as carbon and nitrogen metabolism may be applied in genetic engineering of crops with high stress tolerance, and genetic modification of biofuel crops with high biomass and regulatable lignin biosynthesis

High-throughput deep sequencing reveals that microRNAs play important roles in salt tolerance of euhalophyte Salicornia europaea

BACKGROUND: microRNAs (miRNAs) are implicated in plant development processes and play pivotal roles in plant adaptation to environmental stresses. Salicornia europaea, a salt mash euhalophyte, is a suitable model plant to study salt adaptation mechanisms. S. europaea is also a vegetable, forage, and oilseed that can be used for saline land reclamation and biofuel precursor production on marginal lands. Despite its importance, no miRNA has been identified from S. europaea thus far. RESULTS: Deep sequencing was performed to investigate small RNA transcriptome of S. europaea. Two hundred and ten conserved miRNAs comprising 51 families and 31 novel miRNAs (including seven miRNA star sequences) belonging to 30 families were identified. About half (13 out of 31) of the novel miRNAs were only detected in salt-treated samples. The expression of 43 conserved and 13 novel miRNAs significantly changed in response to salinity. In addition, 53 conserved and 13 novel miRNAs were differentially expressed between the shoots and roots. Furthermore, 306 and 195 S. europaea unigenes were predicted to be targets of 41 conserved and 29 novel miRNA families, respectively. These targets encoded a wide range of proteins, and genes involved in transcription regulation constituted the largest category. Four of these genes encoding laccase, F-box family protein, SAC3/GANP family protein, and NADPH cytochrome P-450 reductase were validated using 5′-RACE. CONCLUSIONS: Our results indicate that specific miRNAs are tightly regulated by salinity in the shoots and/or roots of S. europaea, which may play important roles in salt tolerance of this euhalophyte. The S. europaea salt-responsive miRNAs and miRNAs that target transcription factors, nucleotide binding site-leucine-rich repeat proteins and enzymes involved in lignin biosynthesis as well as carbon and nitrogen metabolism may be applied in genetic engineering of crops with high stress tolerance, and genetic modification of biofuel crops with high biomass and regulatable lignin biosynthesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12870-015-0451-3) contains supplementary material, which is available to authorized users

Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury

BACKGROUND: MicroRNAs have been demonstrated to play an important role in the pathogenesis of diabetic nephropathy (DN). In this study, we investigated both the repertoire of miRNAs in the kidneys of patients with DN and their potential regulatory role in inflammation-mediated glomerular endothelial injury. METHODS: The miRNA expression profiling of the renal biopsy samples was performed by a microarray analysis; then, in situ hybridization and real-time polymerase chain reaction (PCR) were used to determine the localization and expression of two of the miRNAs significantly up-regulated in human DN kidney samples, miR-155 and miR-146a, in the kidney tissues from type 1 and type 2 DN rat models. Human renal glomerular endothelial cells (HRGECs) cultured under high-glucose conditions were transfected with miR-155 and miR-146a mimics, and the transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, and nuclear factor (NF)-κB expressions were examined by western blot, real-time PCR, and an electrophoresis mobility shift assay. RESULTS: The expression of both miR-155 and miR-146a was increased more than fivefold in the kidney samples of the DN patients compared with the controls, and the miR-155 expression was closely correlated with the serum creatinine levels (R = 0.95, P = 0.004). During the induction and progression of the disease in type 1 and type 2 DN rat models, miR-155 and miR-146a were demonstrated to increase gradually. In vitro, high glucose induced the over-expression of miR-155 and miR-146a in the HRGECs, which, in turn, increased the TNF-α, TGF-β1, and NF-κB expression. CONCLUSIONS: Taken together, these findings indicate that the increased expression of miR-155 and miR-146a in the DN patients and in the experimental DN animal models was found to contribute to inflammation-mediated glomerular endothelial injury

Development and evaluation of the Nurotron 26-electrode cochlear implant system.

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world. This article is part of a Special Issue entitled

Development and evaluation of the Nurotron 26-electrode cochlear implant system.

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world. This article is part of a Special Issue entitled

Development and evaluation of the Nurotron 26-electrode cochlear implant system

AbstractAlthough the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world.This article is part of a Special Issue entitled <Lasker Award>