First report of the ectomycorrhizal fungal community associated with two herbaceous plants in Inner Mongolia, China.

Ectomycorrhizal (EM) fungi play a vital role in ensuring plant health, plant diversity, and ecosystem function. However, the study on fungal diversity and community assembly of EM fungi associated with herbaceous plants remains poorly understood. Thus, in our study, Carex pediformis and Polygonum divaricatum in the subalpine meadow of central Inner Mongolia, China were selected for exploring EM fungal diversity and community assembly mechanisms by using llumina MiSeq sequencing of the fungal internal transcribed spacer 2 region (ITS2). We evaluated the impact of soil, climatic, and spatial variables on EM fungal diversity and community turnover. Deterministic vs. stochastic processes for EM fungal community assembly were quantified using ß-Nearest taxon index scores. The results showed that a total of 70 EM fungal OTUs belonging to 21 lineages were identified, of which Tomentella-Thelephora, Helotiales1, Tricholoma, Inocybe, Wilcoxina were the most dominant EM fungal lineages. EM fungal communities were significantly different between the two herbaceous plants and among the two sampling sites, and this difference was mainly influenced by soil organic matter (OM) content and mean annual precipitation (MAP). The neutral community model (NCM) explained 45.7% of the variations in EM fungi community assembly. A total of 99.27% of the ß-Nearest Taxa Index (ßNTI) value was between -2 and 2. These results suggest that the dominant role of stochastic processes in shaping EM fungal community assembly. In addition, RCbray values showed that ecological drift in stochastic processes dominantly determined community assembly of EM fungi. Overall, our study shed light on the EM fungal diversity and community assembly associated with herbaceous plants in the subalpine region of central Inner Mongolia for the first time, which provided a better understanding of the role of herbaceous EM fungi.

The Value of CD64 in the Early Diagnosis for Intracranial Infection After Craniocerebral Surgery.

PURPOSE: To investigate the value of CD64 in the early diagnosis of intracranial infection after craniocerebral surgery. METHODS: A total of 93 patients who met the inclusion and exclusion criteria after neurosurgery in Lianyungang First People's Hospital and Lianyungang Second People's Hospital were admitted and divided into experimental group with intracranial infection (n = 32) and uninfected control group (n = 61) according to the results of cerebrospinal fluid culture. We performed relevant statistical analysis, drew the receiver operating characteristic curve and calculated area under the curve (AUC). RESULTS: The sensitivity and specificity of the CD64, c-reactive protein (CRP), and white blood cell (WBC) counts were 84.38% and 86.89%, 78.13% and 75.41%, and 75.00% and 67.21%, respectively; the AUCs were 0.912, 0.858, and 0.851, respectively. Accuracy was the highest when the 3 diagnosis were combined, reaching 93.75%; the AUC could reach 0.948. CONCLUSIONS: Serum CD64, CRP, and WBC count in the diagnosis of intracranial infection after craniocerebral surgery were significant. CD64 was more valuable than the others. The diagnostic efficiency could be improved when CD64, CRP, and WBC count were combined.

Soil properties under different ecological restoration modes for the quarry in Yanshan mountains of Hebei province, China.

The ecological environment of quarry mining area is fragile, and the vegetation restoration cycle is long and difficult, so scientific and appropriate artificial vegetation is of great significance to ecological restoration. The purpose of this study was to evaluate the herbaceous and woody vegetation restoration, including Medicago sativa (Me), artificial miscellaneous grass (Mg), Rhus typhina (Rh), fruit orchard (Or) and Pinus tabulaeformis (Pi), to investigate the soil physicochemical properties and the structure of the microbial communities, and to reveal the correlation between them. The results addressed that Medicago sativa and artificial miscellaneous grass had significant effect on soil remediation, which were conducive to scientific and efficient ecological restoration, and could promote ecological restoration in the damaged ecosystems. While, the modes of Rh and Pi were not suitable for ecological restoration in this study area because they had strong allelopathy. Another arborous restoration mode of Or showed a better improvement effect (including soil nutrients, soil microbial diversity, etc.) than that of Rh and Pi. The findings also indicated that the herbaceous vegetation restoration modes of Me and Mg significantly increased the relative abundance of Proteobacteria, Acidobacteria, Actinobacteria bacteria, Ascomycota and Mortierllomycota fungi, and reduced the relative abundance of Firmicutes bacteria and Basidiomycota fungi. This study also revealed that the trend of bacterial localization in the fruit orchard, artificial miscellaneous grass and Medicago sativa was more obvious. Among many soil abiotic factors, the contents of organic matter, available nitrogen and pH were the most important factors affecting soil microbial community.

Distribution and phylogeography of the genus Mattirolomyces with a focus on the Asian M. terfezioides haplotypes.

Mattirolomyces is an edible commercial sequestrate genus that is globally distributed. From the five described taxa of this genus, Mattirolomyces terfezioides is the most common species in Asia. Our recent attempts to locate M. terfezioides outside its current distribution area in China documented its first records in areas of poplar trees with the lowest known temperature and precipitation averages ever recorded for this species. This peculiar ecology was not reflected on the species-morphological features nor on its phylogenetic position in the genus. The first attempt to apply the phylogenetic network approach to Mattirolomyces revealed its geographic origin in the Asian-Pacific areas prior to frequent long-distance migration events. Based on data from recent study areas, we found that the collections from Inner Mongolia and the Shanxi province were similar to European collections. Asian haplotypes were less distant from the outgroup comparing to collections from Europe, supporting the hypothesis that M. terfezioides was originated from this Chinese area and was subsequently transported to Europe. Exploring M. terfezioides ecology and its mycorrhiza potential to grow in association with poplars would be of great importance for planning cultivation projects of this valuable desert truffle species in Central and Eastern China, a currently underexploited economic sector that deserves further ecological and M. terfezioides mycorrhizal synthesis investigations.

Stochastic processes dominate community assembly of ectomycorrhizal fungi associated with Picea crassifolia in the Helan Mountains, China.

Introduction: Understanding the underlying mechanisms of microbial community assembly is a fundamental topic in microbial ecology. As an integral part of soil organisms, ectomycorrhizal (EM) fungi play vital roles in ecosystems. Picea crassifolia is an important pine species in the Helan Mountains in Inner Mongolia, China, with high ecological and economic values. However, studies of EM fungal diversity and mechanisms underlying community assembly on this pine species are limited. Methods: In this study, we investigated EM fungal communities associated with P. crassifolia from 45 root samples across three sites in the Helan Mountains using Illumina Miseq sequencing of the fungal rDNA ITS2 region. Results: A total of 166 EM fungal OTUs belonging to 24 lineages were identified, of which Sebacina and Tomentella-Thelephora were the most dominant lineages. Ordination analysis revealed that EM fungal communities were significantly different among the three sites. Site/fungus preference analysis showed that some abundant EM fungal OTUs preferred specific sites. Ecological process analysis implied that dispersal limitation and ecological drift in stochastic processes dominantly determined the community assembly of EM fungi. Discussion: Our study indicates that P. crassifolia harbors a high EM fungal diversity and highlights the important role of the stochastic process in driving community assembly of mutualistic fungi associated with a single plant species in a semi-arid forest in northwest China.

Ectomycorrhizal fungal communities associated with Larix gemelinii Rupr. in the Great Khingan Mountains, China.

Larix gemelinii is an important tree species in the Great Khingan Mountains in Northeast China with a high economic and ecological value for its role in carbon sequestration and as a source of lumber and nuts. However, the ectomycorrhizal (EM) fungal diversity and community composition of this tree remain largely undefined. We examined EM fungal communities associated with L. gemelinii from three sites in the Great Khingan Mountains using Illumina Miseq to sequence the rDNA ITS2 region and evaluated the impact of spatial, soil, and climatic variables on the EM fungal community. A total of 122 EM fungal operational taxonomic units (OTUs) were identified from 21 pooled-root samples, and the dominant EM fungal lineages were /tricholoma, /tomentella-thelephora, /suillus-rhizopogon, and /piloderma. A high proportion of unique EM fungal OTUs were present; some abundant OTUs largely restricted to specific sites. EM fungal richness and community assembly were significantly correlated with spatial distance and climatic and soil variables, with mean annual temperature being the most important predictor for fungal richness and geographic distance as the largest determinant for community turnover. Our findings indicate that L. gemelinii has a rich and distinctive EM fungal community contributing to our understanding of the montane EM fungal community structure from the perspective of a single host plant that has not been previously reported.

Fungal Diversity and Community Assembly of Ectomycorrhizal Fungi Associated With Five Pine Species in Inner Mongolia, China.

Ectomycorrhizal (EM) fungi play vital roles in ensuring host plants' health, plant diversity, and the functionality of the ecosystem. However, EM fungal diversity, community composition, and underlying assembly processes in Inner Mongolia, China, where forests are typically semiarid and cold-temperate zones, attract less attention. In this study, we investigated EM fungal communities from 63 root samples of five common pine plants in Inner Mongolia across 1,900 km using Illumina Miseq sequencing of the fungal internal transcribed spacer 2 region. We evaluated the impact of host plant phylogeny, soil, climatic, and spatial variables on EM fungal diversity and community turnover. Deterministic vs. stochastic processes for EM fungal community assembly were quantified using ß-nearest taxon index scores. In total, we identified 288 EM fungal operational taxonomic units (OTUs) belonging to 31 lineages, of which the most abundant lineages were Tomentella-Thelephora, Wilcoxina, Tricholoma, and Suillus-Rhizopogon. Variations in EM fungal OTU richness and community composition were significantly predicted by host phylogeny, soil (total nitrogen, phosphorus, nitrogen-phosphorus ratio, and magnesium), climate, and spatial distance, with the host plant being the most important factor. ß-nearest taxon index demonstrated that both deterministic and stochastic processes jointly determined the community assembly of EM fungi, with the predominance of stochastic processes. At the Saihanwula site selected for preference analysis, all plant species (100%) presented significant preferences for EM fungi, 54% of abundant EM fungal OTUs showed significant preferences for host plants, and 26% of pairs of plant species and abundant fungal OTUs exhibited remarkably strong preferences. Overall, we inferred that the high diversity and distinctive community composition of EM fungi associated with natural pine species in Inner Mongolia and the stochastic processes prevailed in determining the community assembly of EM fungi. Our study shed light on the diversity and community assembly of EM fungi associated with common pine species in semiarid and cold temperate forests in Inner Mongolia, China, for the first time and provided a better understanding of the ecological processes underlying the community assembly of mutualistic fungi.

Characteristic and phylogenetic analyses of chloroplast genome for Ephedra monosperma (Ephedraceae), an important medicinal species.

Ephedra monosperma is an important medicinal plant of Ephedra (Ephedraceae). The complete chloroplast genome of E. monosperma was assembled from Illumina pair-end sequence reads. The whole chloroplast (cp) genome is 109,548 bp in length and presents a quadripartite structure consisting of two copies of inverted repeat (IR) regions (20,398) separated by a large single copy (LSC) region (60,674 bp) and a small single copy (SSC) region (8078 bp). The cp genome of E. monosperma encodes a total of 118 genes, including 73 protein-coding genes, 37 tRNA genes and 8 rRNA genes. The overall GC content of E. monosperma cp genome is 36.6%. A maximum likelihood (ML) phylogenetic analysis revealed that E. monosperma was close to Ephedra equisetina. The ML tree also showed Ephedraceae appeared more closely related to Gnetaceae than to the other families in Gymnospermae.

Coactosin-Like Protein (COTL1) Promotes Glioblastoma (GBM) Growth in vitro and in vivo.

OBJECTIVE: To assess the expression levels of COTL1 in human GBM tissues and evaluate the potential involvement of COTL1 in cancer progression. METHODS: Bioinformation analysis was performed to evaluate COTL1 mRNA levels in GBM tissues and normal tissues, according to the TCGA database, and explore the effects on prognosis. Immunohistochemical (IHC) assays were performed to evaluate COTL1 expression in human GBM tissues and the clinical pathological analysis was performed. Colony formation and MTT assays were performed to evaluate the effects of COTL1 on GBM cell proliferation. Immunoblot assays were performed to detect the expression level of COTL1, Ki67, and PCNA. A xenograft model was developed in mice to assess the effects of COTL1 on tumor growth in vivo. RESULTS: We found COTL1 had an obvious high expression in human GBM tissues. The expression of COTL1 was related to recurrence (P=0.006**) and prognosis of patients with GBM. Our data further demonstrated COTL1 promoted cell proliferation in vitro and contributed to tumor growth of GBM cells in mice. CONCLUSION: We therefore identified a novel and promising therapeutic target for the treatment of GBM.

Sex-specific association of serum uric acid dynamics with the incidence of metabolic syndrome in a health check-up Chinese population: a prospective cohort study.

OBJECTIVE: Many studies have demonstrated that elevated serum uric acid (SUA) level is linked with metabolic syndrome (MetS). However, whether there is a sex difference in the association between SUA and MetS has not been determined. This study aimed to accurately explore the impact of SUA longitudinal changes on MetS by sex. DESIGN: A prospective cohort study. SETTING: The Health Check-up Centre of the Second Hospital affiliated with Dalian Medical University from 2010 to 2016. PARTICIPANTS: A health check-up cohort of 577 men and 1698 women aged 20-60 years who did not exhibit MetS or hyperuricaemia at baseline and underwent at least two physical examinations from 2010 to 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Weight, height, blood pressure and blood biochemistry parameters, including SUA, were measured. MetS was defined according to the Joint Interim Statement criteria. METHODS: Based on longitudinal data, a linear mixed-effects model was constructed to explore the characteristics of SUA dynamic changes in males and females, and joint modelling of longitudinal and survival data was done to analyse the association between SUA dynamic changes and MetS occurrence. RESULTS: The natural logarithm of SUA (LNSUA) in females exhibited a gradually increasing trend, and its annual growth rate in females who developed MetS was greater than that of the non-MetS females. The longitudinal growth of SUA in females was a risk factor for the onset of MetS, and the estimated HR was 13.2580 (95% CI 1.9106 to 91.9957) for each 1-unit rise in LNSUA longitudinally. An association between the longitudinal growth of LNSUA and MetS was not found in males. CONCLUSIONS: The longitudinal increase in SUA in females could increase the risk of MetS, even if the SUA changes within the normal range. The longitudinal increase in SUA in males was not a predictor for MetS.

An evaluation model for aboveground biomass based on hyperspectral data from field and TM8 in Khorchin grassland, China.

Biomass is an important indicator for monitoring vegetation degradation and productivity. This study tests the applicability of Hyperspectral Remote-Sensing in situ measurements for high-precision estimation aboveground biomass (AGB) on regional scales of Khorchin grassland in Inner Mongolia, China. In order to improve prediction accuracy of AGB which is frequently used as an indicator of aboveground net primary productivity (ANPP), this paper combined ground measurement with remote sensing inversion to build the spectral model. The ground normalized difference vegetation index (SOC_NDVI) calculated from ground spectral of grassland vegetation which was measured by a portable visible/NIR hyperspectral spectrometer (SOC 710). Meanwhile, the remote normalized difference vegetation index (TM_NDVI) calculated from remote spectral of grassland vegetation which was measured by Thematic Mapper (TM) from Landsat 8 which launched by National Aeronautics and Space Administration (NASA). According to regression analysis for the relationship between AGB and SOC_NDVI, SOC_NDVI and TM_NDVI, the evaluation model for aboveground biomass was developed (AGB = 12.523×e3.370×(0.462×TM_NDVI+0.413), standard error = 24.74 g m-2, R2 = 0.636, p < 0.001). The model accuracy verification results show that the correlation between the measured value and the predicted value of biomass was better with low model standard error. The model could make up for the lack of timeliness and comprehensiveness of conventional ground biomass survey, and provide technical support for high-precision large-area productivity estimation and ecological degradation diagnosis of regional scale grassland.

Assessing the naturalness of a restored coal mine area on the Loess Plateau, China.

The Loess Plateau in China is an important area for mineral resources and therefore heavily exploited. As a measure to solve the conflict between conservation and development, ecological restoration has attracted more and more attention. More methods are needed to assess their effectiveness in achieving ecological and social goals. To adequately assess the effectiveness of natural restoration, the naturalness index (NI) has been developed to evaluate restoration effectiveness based on the Soil nutrient index (SNI), community composition index (CCI), and community succession index (CSI). By developing and applying of the NI to an open-pit mining area on Loess plateau, northwest China, the results show that: (i) In the study area, the cumulative dominance index of perennial grasses, the community function index, soil organic matter, and soil hydrolysable nitrogen greatly explained the community development. (ii) All the indicators values have changed with the increase of revolution time, the value of SNI increase obviously than the CCI and CSI comparing with the control plot, which indicated that the soil nutrient could be completely restored more easily. (iii) According to the Logistic Growth Model between NI and restoration time, it can be deduced that an ecosystem similar to the original ecosystem could be established after about 29 years of natural restoration.

The longitudinal increments of serum alanine aminotransferase increased the incidence risk of metabolic syndrome: A large cohort population in China.

BACKGROUND: Although alanine aminotransferase (ALT) is well known to be associated with metabolic syndrome (MetS), prospective data on longitudinal increments in ALT activities and incident cases of MetS are limited. We analyzed the impact of longitudinal increments of ALT on MetS based on a health check-up population in China. METHODS: A total of 4491 subjects free of MetS who completed at least two annual health examinations during March 2010 to April 2016 were enrolled in this cohort study. The MetS was defined according to the Joint Interim Statement criteria 2009. The RRs of incident MetS were estimated by using the Cox model and the Joint model in R software. RESULTS: The cumulative incidence of MetS was 18.55% during the 7 years of follow-up. In the Cox model, the estimated RR of developing MetS was 1.751 (95% CI =1.532-2.000) for 1 unit augmented in LNALT-0 level. In the Joint model, the estimated RR of developing MetS was 3.626 (95% CI = 2.721-4.831) for 1 unit augmented in LNALT activity longitudinally. CONCLUSIONS: The longitudinal increment of individuals' ALT activity over time increased the incidence risk of MetS and the effects generated by longitudinal increments of ALT on MetS was higher than that generated by baseline ALT.

Longitudinal associations of high-density lipoprotein cholesterol or low-density lipoprotein cholesterol with metabolic syndrome in the Chinese population: a prospective cohort study.

OBJECTIVE: Currently, most studies only reveal the relationship between baseline high-density lipoprotein cholesterol (HDL-c) or low-density lipoprotein cholesterol (LDL-c) levels and metabolic syndrome (MetS). The relationship between dynamic changes in HDL-c or LDL-c and MetS remains unclear. We aimed to gain a deeper understanding of the relationship between the dynamic changes in HDL-c or LDL-c and MetS. DESIGN: A prospective study. SETTING: The Medical Centre of the Second Hospital affiliated with Dalian Medical University from 2010 to 2016. PARTICIPANTS: A total of 4542 individuals who were initially MetS-free and completed at least two follow-up examinations as part of the longitudinal population were included. METHODS: The Joint Interim Statement criteria 2009 were used to define MetS. We used the Joint model to estimate the relative risks (RRs) of incident MetS. RESULTS: The cumulative incidence of MetS was 17.81% and was 14.86% in men and 5.36% in women during the 7 years of follow-up. In the Joint models, the RRs of the longitudinal decrease in HDL-c and the longitudinal increase in LDL-c for the development of MetS were 18.8781-fold (95% CI 12.5156 to 28.4900) and 1.3929-fold (95% CI 1.2283 to 1.5795), respectively. CONCLUSIONS: The results highlight that the dynamic longitudinal decrement of HDL-c or the increment of LDL-c is associated with an elevated risk of MetS.

DNA methylation in schizophrenia in different patient-derived cell types.

DNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells may reflect a "ground state" upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences. Fibroblasts provide a non-neural control for life-long developmental and environmental influences. Genome-wide profiling of DNA methylation and gene expression was done in these three cell types from the same individuals. All cell types had distinct, statistically significant schizophrenia-associated differences in DNA methylation and linked gene expression, with Gene Ontology analysis showing that the differentially affected genes clustered in networks associated with cell growth, proliferation, and movement, functions known to be affected in schizophrenia patient-derived cells. Only five gene loci were differentially methylated in all three cell types. Understanding the role of epigenetics in cell function in the brain in schizophrenia is likely to be complicated by similar cell type differences in intrinsic and environmentally induced epigenetic regulation.

Cell migration in schizophrenia: Patient-derived cells do not regulate motility in response to extracellular matrix.

Schizophrenia is a highly heritable psychiatric disorder linked to a large number of risk genes. The function of these genes in disease etiology is not fully understood but pathway analyses of genomic data suggest developmental dysregulation of cellular processes such as neuronal migration and axon guidance. Previous studies of patient-derived olfactory cells show them to be more motile than control-derived cells when grown on a fibronectin substrate, motility that is dependent on focal adhesion kinase signaling. The aim of this study was to investigate whether schizophrenia patient-derived cells are responsive to other extracellular matrix (ECM) proteins that bind integrin receptors. Olfactory neurosphere-derived cells from nine patients and nine matched controls were grown on ECM protein substrates at increasing concentrations and their movement was tracked for 24h using automated high-throughput imaging. Control-derived cells increased their motility as the ECM substrate concentration increased, whereas patient-derived cell motility was little affected by ECM proteins. Patient and control cells had appropriate integrin receptors for these ECM substrates and detected them as shown by increases in focal adhesion number and size in response to ECM proteins, which also induced changes in cell morphology and cytoskeleton. These observations indicate that patient cells failed to translate the detection of ECM proteins into appropriate changes in cell motility. In a sense, patient cells act like a moving car whose accelerator is jammed, moving at the same speed without regard to the external environment. This focuses attention on cell motility regulation rather than speed as key to impairment of neuronal migration in the developing brain in schizophrenia.

Schizophrenia patient-derived olfactory neurosphere-derived cells do not respond to extracellular reelin.

Reelin expression is reduced in various regions in the post-mortem brain of schizophrenia patients but the exact role of reelin function in the neurobiology of schizophrenia remains elusive. Absence of reelin in knockout mouse causes inverted lamination of the neocortex due to aberrant neuronal migration. The aim of this study was to utilize patient-derived olfactory neurosphere-derived (ONS) cells to investigate whether extracellular reelin alters cell motility in schizophrenia patient-derived cells. ONS cells from nine patients were compared with cells from nine matched healthy controls. Automated high-throughput imaging and analysis were used to track motility of individual living cells on reelin-coated surfaces produced from reelin secreted into the medium by HEK293FT cells transfected with the full-length reelin plasmid pCrl. Automated assays were used to quantify intracellular cytoskeleton composition, cell morphology, and focal adhesions. Expression of reelin and components of the reelin signaling pathway were measured by western blot and flow cytometry. Reelin inhibited the motility of control cells but not patient cells, and increased the number and size of focal adhesions in control cells but not patient cells. Patient and control cells expressed similar levels of the reelin receptors and the reelin signaling protein, Dab1, but patient cells expressed less reelin. Patient cells were smaller than control cells and had less actin and acetylated α-tubulin, components of the cytoskeleton. These findings are the first direct evidence that cellular responses to reelin are impaired in schizophrenia and are consistent with the role of reelin in cytoarchitectural deficits observed in schizophrenia patient brains.

Mechanism of impaired microtubule-dependent peroxisome trafficking and oxidative stress in SPAST-mutated cells from patients with Hereditary Spastic Paraplegia.

Hereditary spastic paraplegia (HSP) is an inherited neurological condition that leads to progressive spasticity and gait abnormalities. Adult-onset HSP is most commonly caused by mutations in SPAST, which encodes spastin a microtubule severing protein. In olfactory stem cell lines derived from patients carrying different SPAST mutations, we investigated microtubule-dependent peroxisome movement with time-lapse imaging and automated image analysis. The average speed of peroxisomes in patient-cells was slower, with fewer fast moving peroxisomes than in cells from healthy controls. This was not because of impairment of peroxisome-microtubule interactions because the time-dependent saltatory dynamics of movement of individual peroxisomes was unaffected in patient-cells. Our observations indicate that average peroxisome speeds are less in patient-cells because of the lower probability of individual peroxisome interactions with the reduced numbers of stable microtubules: peroxisome speeds in patient cells are restored by epothilone D, a tubulin-binding drug that increases the number of stable microtubules to control levels. Patient-cells were under increased oxidative stress and were more sensitive than control-cells to hydrogen peroxide, which is primarily metabolised by peroxisomal catalase. Epothilone D also ameliorated patient-cell sensitivity to hydrogen-peroxide. Our findings suggest a mechanism for neurodegeneration whereby SPAST mutations indirectly lead to impaired peroxisome transport and oxidative stress.

Glutamatergic and central cholinergic dysfunction in the CA1, CA2 and CA3 fields on spatial learning and memory in chronic cerebral ischemia-Induced vascular dementia of rats.

Chronic cerebral ischemia (CCI) is associated with cognitive decline in aging, vascular dementia and Alzheimer's disease. Substantial evidence has shown that chronic cerebral ischemia may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood so far. In the present study, we used a rat model of chronic cerebral ischemia by permanent bilateral common carotid artery occlusion (BCCAO) to investigate the alterations of glutamatergic and central cholinergic dysfunction, and their causal relationship with the cognitive deficits induced by chronic cerebral ischemia. We found that BCCAO rats exhibited spatial learning and memory impairments dysfunction 3 month after BCCAO. Meanwhile, vGluT levels as well as glutamatergic and central cholinergic positive neurons in the hippocampus CA1-3 field significantly decreased. The protection of glutamergic and cholinergic neurons or regulating glutamate and central cholinergic levels in hippocampal subregion may have beneficial effects on cognitive impairments associated with the possible mechanism in CCI-induced vascular dementia.

Oncogenic Myc Induces Expression of Glutamine Synthetase through Promoter Demethylation.

c-Myc is known to promote glutamine usage by upregulating glutaminase (GLS), which converts glutamine to glutamate that is catabolized in the TCA cycle. Here we report that in a number of human and murine cells and cancers, Myc induces elevated expression of glutamate-ammonia ligase (GLUL), also termed glutamine synthetase (GS), which catalyzes the de novo synthesis of glutamine from glutamate and ammonia. This is through upregulation of a Myc transcriptional target thymine DNA glycosylase (TDG), which promotes active demethylation of the GS promoter and its increased expression. Elevated expression of GS promotes cell survival under glutamine limitation, while silencing of GS decreases cell proliferation and xenograft tumor growth. Upon GS overexpression, increased glutamine enhances nucleotide synthesis and amino acid transport. These results demonstrate an unexpected role of Myc in inducing glutamine synthesis and suggest a molecular connection between DNA demethylation and glutamine metabolism in Myc-driven cancers.