Intranasal deferoxamine attenuates synapse loss via up-regulating the P38/HIF-1α pathway on the brain of APP/PS1 transgenic mice

AbstractThe widely recognized neuroprotective effect of iron chelators is contributed by their ability to prevent reactive oxygen species generation via the Fenton reaction, which sequesters redox-active Fe. An additional neuroprotective mechanism of iron-chelating compounds is to regulate the transcriptional activator hypoxia-inducible factor 1α (HIF-1α). In the present study, we observed that intranasal administration of deferoxamine decreased beta-amyloid (Aβ) deposition and rescued synapse loss in the brain of Aβ precursor protein and presenilin-1 (APP/PS1) double transgenic mice. We found that DFO up-regulated HIF-1α mRNA expression and its protein level, and further induced the proteins that are encoded from HIF-1-adaptive genes, including transferrin receptor (TFR), divalent metal transporter 1 (DMT1), and brain-derived neurotrophic factor (BDNF). The effects of DFO on the induction and stabilization of HIF-1α were further confirmed in vitro. This was accompanied by a decrease of Fe in the CA3 region of the hippocampus. Western blotting studies revealed that DFO differentially enhanced the phosphorylation of mitogen-activated protein kinase (MAPK) /P38 kinase in vitro and in vivo. The results suggest that the DFO may up-regulate several HIF-1-dependent neuroprotective-adaptive genes in AD via activating P38/HIF-1α pathway, which may serve as important therapeutic targets to the disease

Similarities and Differences in Decision-Making Impairments between Autism Spectrum Disorder and Schizophrenia

Although individuals with autism spectrum disorders (ASD) and schizophrenia (SCH) share overlapping characteristics and may perform similarly on many cognitive tasks, cognitive dysfunctions common to both disorders do not necessarily share the same underlying mechanisms. Decision making is currently a major research interest for both ASD and SCH. The aim of the present study was to make direct comparisons of decision making and disorder-specific underlying neuropsychological mechanisms between the two disorders. Thirty-seven participants with ASD, 46 patients with SCH and 80 healthy controls (HC) were assessed with the Iowa Gambling Task (IGT), which measures decision-making under ambiguity, and the Game of Dice Task (GDT), which measures decision-making under risk. The results revealed that both the ASD and SCH groups had deficits for both the IGT and GDT compared with the HC. More importantly, in the IGT, participants with ASD displayed a preference for deck A, indicating that they had more sensitivity to the magnitude of loss than to the frequency of loss, whereas patients with SCH displayed a preference for deck B, indicating that they showed more sensitivity to the frequency of loss than to the magnitude of loss. In the GDT, the impaired performance might be due to the deficits in executive functions in patients with SCH, whereas the impaired performance might be due to the deficits in feedback processing in participants with ASD. These findings demonstrate that there are similar impairments in decision-making tasks between ASD and SCH; however, these two disorders may have different impairment mechanisms

Bioaugmentation with endophytic bacterium E6S homologous to Achromobacter piechaudii enhances metal rhizoaccumulation in host Sedum plumbizincicola

Application of hyperaccumulator–endophyte symbiotic systems is a potential approach to improve phytoremediation efficiency, since some beneficial endophytic bacteria are able to detoxify heavy metals, alter metal solubility in soil and facilitate plant growth. The objective of this study was to isolate multi-metal resistant and plant beneficial endophytic bacteria and to evaluate their role in enhancing plant growth and metal accumulation/translocation. The metal resistant endophytic bacterial strain E6S was isolated from stems of the Zn/Cd hyperaccumulator plant Sedum plumbizincicola growing in metalliferous mine soils using Dworkin and Foster salts minimal agar medium with 1-aminocyclopropane-1-carboxylate (ACC) as the sole nitrogen source, and identified as homologous to Achromobacter piechaudii based on morphological and biochemical characteristics, partial 16S rDNA sequence and phylogenetic analysis. Strain E6S showed high level of resistance to various metals (Cd, Zn and Pb). Besides utilizing ACC, strain E6S exhibited plant beneficial traits, such as solubilization of phosphate and production of indole-3-acetic acid. Inoculation with E6S significantly increased the bioavailability of Cd, Zn and Pb in soil. In addition, bacterial cells bound considerable amounts of metal ions in the following order: Zn ˃ Cd ˃ Pb. Inoculation of E6S significantly stimulated plant biomass, uptake and bioaccumulation of Cd, Zn and Pb. However, E6S greatly reduced the root to shoot translocation of Cd and Zn, indicating that bacterial inoculation assisted the host plant to uptake and store heavy metals in its root system. Inoculation with the endophytic bacterium E6S homologous to A. piechaudii can improve phytostabilization of metalliferous soils due to its effective ability to enhance in situ metal rhizoaccumulation in plants

A combination of biochar-mineral complexes and compost improves soil bacterial processes, soil quality and plant properties

Organic farming avoids the use of synthetic fertilizers and promises food production with minimal environmental impact, however this farming practice does not often result in the same productivity as conventional farming. In recent years, biochar has received increasing attention as an agricultural amendment and by coating it with minerals to form biochar-mineral complex (BMC) carbon retention and nutrient availability can be improved. However, little is known about the potential of BMC in improving organic farming. We therefore investigated here how soil, bacterial and plant properties respond to a combined treatment of BMC and an organic fertilizer, i.e. a compost based on poultry manure. In a pakchoi pot trial, BMC and compost showed synergistic effects on soil properties, and specifically by increasing nitrate content. Soil nitrate has been previously observed to increase leaf size and we correspondingly saw an increase in the surface area of pakchoi leaves under the combined treatment of BMC and chicken manure. The increase in soil nitrate was also correlated with an enrichment of bacterial nitrifiers due to BMC. Additionally, we observed that the bacteria present in the compost treatment had a high turnover, which likely facilitated organic matter degradation and a reduction of potential pathogens derived from the manure. Overall our results demonstrate that a combination of BMC and compost can stimulate microbial process in organic farming that result in better vegetable production and improved soil properties for sustainable farming

Chemolithoautotrophic arsenite oxidation by a thermophilic Anoxybacillus flavithermus TCC9-4 from hot spring in Tengchong of Yunnan, China

A new facultative chemolithoautotrophic arsenite-oxidizing bacterium TCC9-4 was isolated from a hot spring microbial mat in Tengchong of Yunnan, China. This strain could grow with arsenite (AsIII) as an energy source, CO2-HCO3- as a carbon source and oxygen as the electron acceptor in a minimal salts medium. Under chemolithoautotrophic conditions, more than 90 % of 100 mg/L AsIII could be oxidized by the strain TCC9-4 in 36 hours. Temperature was an important environmental factor that strongly influenced AsIII oxidation rate and AsIII oxidase (Aio) activity; highest Aio activity was found at the optimal temperature of 40 oC. Addition of 0.01 % yeast extract enhanced the growth significantly, but delayed the AsIII oxidation. On the basis of 16S rDNA phylogenetic sequence analysis, strain TCC9-4 was identified as Anoxybacillus flavithermus. To our best knowledge, this is the first report of arsenic oxidation by Anoxybacillus flavithermus. The results of this study expand our current understanding of microbially-mediated arsenic oxidation in hot spring

Expression of a codon-optimized dsdA gene in tobacco plastids and rice nuclear confers D-serine tolerance

D-serine is toxic to plants. D-serine ammonia lyase, which is encoded by the dsdA gene, can attenuate this toxicity with high specificity. In the present study, we explored the function of codon-optimized dsdA with tobacco plastids and rice nuclear transformation system. It was shown that the dsdA gene was site-specifically integrated into the tobacco chloroplast genome and displayed a high level of expression. Genetic analysis of the progenies showed that the dsdA gene is maternally inherited and confers sufficient D-serine resistance in tobacco. The effective screening concentrations of D-serine for seed germination, callus regeneration and foliar spray were 10 mM, 30 mM and 75 mM, respectively. In addition, calluses from homozygous transgenic rice lines also showed significant tolerance to D-serine (up to 75 mM). Our study proves the feasibility of using dsdA gene as a selectable marker in both chloroplast and nuclear transformation systems

Age and Racial Differences Among PSA-Detected (AJCC Stage T1cN0M0) Prostate Cancer in the U.S.: A Population-Based Study of 70,345 Men

Purpose: Few studies have evaluated the risk profile of PSA-detected T1cN0M0 prostate cancer, defined as tumors diagnosed by needle biopsy because of elevated PSA levels without other clinical signs of disease. However, some men with stage T1cN0M0 prostate cancer may have high-risk disease, thus experiencing inferior outcomes as predicted by a risk group stratification model.Methods: We identified men diagnosed with stage T1cN0M0 prostate cancer from 2004-2008 reported to the SEER program. Multivariate logistic regression was used to model the probability of intermediate-risk (PSA >10 ng/ml but < 20 ng/ml and/or GS 7), and high-risk disease (PSA >20 ng/ml, and/or GS ≥8), relative to low-risk disease (PSA <10 ng/ml and GS ≤6), adjusting for age, race, marital status, median household income, and area of residence. Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were identified. Of these, 47.6%, 35.9%, and 16.5% presented with low-, intermediate-, and high-risk disease, respectively. At baseline (50 years of age), risk was higher for black men than for whites for high-risk disease (OR 3.31, 95% CI 2.85-3.84). The ORs for age (per year) for high-risk disease relative to low-risk disease were 1.09 (95% CI 1.09-1.10) for white men, and as 1.06 (95% CI 1.05-1.07) for black men. Further, among a subgroup of men with low PSA (<10 ng/ml) T1cN0M0 prostate cancer, risk was also higher for black man than for white men at baseline (50 years of age) (OR 2.70, 95% CI 2.09-3.48). The ORs for age (per year) for high-risk disease relative to low-risk disease were 1.09 (95% CI 1.09-1.10) for white men, and as 1.06 (95% CI 1.05-1.07) for black men.Conclusions: A substantial proportion of men with PSA-detected prostate cancer as reported to the SEER program had high-risk disease. Black race and older age were associated with a greater likelihood of high-risk disease

Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study

Heshouwu (HSW), the dry roots of Polygonum multiflorum, a classical traditional Chinese medicine is used as a tonic for a wide range of conditions，particularly those associated with aging. However, it tends to be taken overdose or long term in these years, which has resulted in liver damage reported in many countries. In this study, the indicative roles of nine bile acids (BAs) were evaluated to offer potential biomarkers for HSW induced liver injury. Nine BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA) in rat bile and serum were detected by a developed LC-MS method after 42 days treatment. Partial least square-discriminate analysis (PLS-DA) was applied to evaluate the indicative roles of the nine BAs, and metabolism of the nine BAs was summarized. Significant change was observed for the concentrations of nine BAs in treatment groups compared with normal control; In the PLS-DA plots of nine BAs in bile, normal control and raw HSW groups were separately clustered and could be clearly distinguished, GDCA was selected as the distinguished components for raw HSW overdose treatment group. In the PLS-DA plots of nine BAs in serum, the normal control and raw HSW overdose treatment group were separately clustered and could be clearly distinguished, and HDCA was selected as the distinguished components for raw HSW overdose treatment group. The results indicated the perturbation of nine BAs was associated with HSW induced liver injury; GDCA in bile, as well as HDCA in serum could be selected as potential biomarkers for HSW induced liver injury; it also laid the foundation for the further search on the mechanisms of liver injury induced by HSW

Overexpression of an Apocynum venetum DEAD-box helicase gene (AvDH1) in cotton confers salinity tolerance and increases yield in a saline field

Soil salinity is a major environmental stress limiting plant growth and productivity. We have reported previously the isolation of an Apocynum venetum DEAD-box helicase 1 (AvDH1) that is expressed in response to salt exposure. Here, we report that the overexpression of AvDH1 driven by a constitutive cauliflower mosaic virus-35S promoter in cotton plants confers salinity tolerance. Southern and northern blotting analyses showed that the AvDH1 gene was integrated into the cotton genome and expressed. In this study, the growth of transgenic cotton expressing AvDH1 was evaluated under saline conditions in a growth chamber and in a saline field trial. Transgenic cotton overexpressing AvDH1 was much more resistant to salt than the wild-type plants when grown in a growth chamber. The lower membrane ion leakage, along with increased activity of superoxide dismutase (SOD), in AvDH1 transgenic lines suggested that these characteristics may prevent membrane damage, which increases plant survival rates. In a saline field, the transgenic cotton lines expressing AvDH1 showed increased boll numbers, boll weights and seed cotton yields compared with wild-type plants, especially at high soil salinity levels. This study indicates that transgenic cotton expressing AvDH1 is a promising option for increasing crop productivity in saline fields

Depression-like behavior induced by nesfatin-1 in rats: involvement of increased immune activation and imbalance of synaptic vesicle proteins

Depression is a multicausal disorder and has been associated with metabolism regulation and immuno-inflammatory reaction. The anorectic molecule nesfatin-1 has recently been characterized as a potential mood regulator, but its precise effect on depression and the possible mechanisms remain unknown, especially when given peripherally. In the present study, nesfatin-1 was intraperitoneally injected to the rats and the depression-like behavior and activity of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated. The plasma concentrations of nesfatin-1, interleukin 6 (IL-6), and C-reactive protein (CRP); and the hypothalamic expression levels of nesfatin-1, synapsinⅠ, and synaptotagminⅠmRNA were evaluated in nesfatin-1 chronically treated rats. The results showed that both acute and chronic administration of nesfatin-1 increased immobility in the forced swimming test (FST), and resulted in the hyperactivity of HPA axis, as indicated by the increase of plasma corticosterone concentration and hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Moreover, after chronic nesfatin-1 administration, the rats exhibited decreased activity and exploratory behavior in the open field test (OFT) and increased mRNA expression of synapsinⅠand synaptotagminⅠin the hypothalamus. Furthermore, chronic administration of nesfatin-1 elevated plasma concentrations of IL-6 and CRP, which were positively correlated with despair behavior, plasma corticosterone level, and the hypothalamic mRNA expression of synapsinⅠ and synaptotagminⅠ. These results indicated that exogenous nesfatin-1 could induce the immune-inflammatory activation，which might be a central hug linking the depression-like behavior and the imbalanced mRNA expression of synaptic vesicle proteins in the hypothalamus