BACKGROUND Chemoautotrophic ammonia oxidizing bacteria (AOB) have the metabolic ability to oxidize ammonia to nitrite aerobically. This metabolic feature has been widely used, in combination with denitrification, to remove nitrogen from wastewater in wastewater treatment plants (WWTPs). However, the relative influence of specific deterministic environmental factors to AOB community dynamics in WWTP is uncertain. The ecological principles underlying AOB community dynamics and nitrification stability and how they are related are also poorly understood. METHODOLOGY/PRINCIPAL FINDINGS The community dynamics of ammonia oxidizing bacteria (AOB) in a pilot-scale WWTP were monitored over a one-year period by Terminal Restriction Fragment Length Polymorphism (T-RFLP). During the study period, the effluent ammonia concentrations were almost below 2 mg/L, except for the first 60 days, indicting stable nitrification. T-RFLP results showed that, during the test period with stable nitrification, the AOB community structures were not stable, and the average change rate (every 15 days) of AOB community structures was 10%±8%. The correlations between T-RFLP profiles and 10 operational and environmental parameters were tested by Canonical Correlation Analysis (CCA) and Mantel test. The results indicated that the dynamics of AOB community correlated most strongly with Dissolved Oxygen (DO), effluent ammonia, effluent Biochemical Oxygen Demand (BOD) and temperature. CONCLUSIONS/SIGNIFICANCE This study suggests that nitrification stability is not necessarily accompanied by a stable AOB community, and provides insight into parameters controlling the AOB community dynamics within bioreactors with stable nitrification.

BACKGROUND: First-degree relatives (FDRs) of early-onset gastric carcinoma (EOGC) patients are at increased risk of cancer development. OLGA/OLGIM (Operative Link on Gastritis/Intestinal Metaplasia Assessment) classifications have been proposed for the identification of individuals at high risk of gastric cancer development. AIM: To estimate the prevalence and severity of premalignant conditions and lesions in FDRs of EOGC patients. METHODS: A case-control study was conducted encompassing 103 FDRs of EOGC patients (cases) and 101 age- and gender-matched controls, all submitted to upper GI endoscopy and OLGA and OLGIM used for staging as well as modified versions with exclusion of the biopsies from incisura angularis in the analysis. RESULTS: Helicobacter pylori infection was present in 82% of cases (P = 0.001). Atrophy was present in 70% of cases (OLGA stages I-IV). High-risk stages (III-IV) were identified only in cases (19%)(P < 0.001). Dysplasia was diagnosed only in cases (n = 7, P = 0.007). The application of OLGIM, modified OLGA and modified OLGIM classifications led to downgrade of stages in comparison with the original OLGA classification (27%, 15% and 30% respectively). In all classification systems, dysplastic lesions clustered (86%) in high-risk stages. CONCLUSIONS: FDRs of EOGC patients have, even at young ages, a high prevalence of H. pylori infection, high-risk OLGA and OLGIM stages and dysplasia. These patients should undergo accurate endoscopic observation with at least four biopsies in antrum and corpus to allow adequate staging and follow-up of premalignant conditions and lesions scored in high-risk stages, in accordance with international guidelines recently proposed.

ABSTRACT: BACKGROUND: Type-2 Diabetes is a major health concern in the United States and other Westernized countries, with prevalence increasing yearly. There is a need to better model and predict adverse drug reactions, drug-induced liver injury, and drug efficacy in this population. Because transporters significantly contribute to drug clearance and disposition, it is highly significant to determine whether a severe diabetes phenotype alters drug transporter expression, and whether diabetic mouse models have altered disposition of acetaminophen (APAP) metabolites. RESULTS: Transporter mRNA and protein expression were quantified in livers and kidneys of adult C57BKS and db/db mice, which have a severe diabetes phenotype due to a lack of a functional leptin receptor. The urinary excretion of acetaminophen-glucuronide, a substrate for multidrug resistance-associated proteins transporters was also determined. The mRNA expression of major uptake transporters, such as organic anion transporting polypeptide Slco1a1 in liver and kidney, 1a4 in liver, and Slc22a7 in kidney was decreased in db/db mice. In contrast, Abcc3 and 4 mRNA and protein expression was more than 2 fold higher in db/db male mouse livers as compared to C57BKS controls. Urine levels of APAP-glucuronide,-sulfate, and N-acetyl cysteine metabolites were higher in db/db mice. CONCLUSION: A severe diabetes phenotype/presentation significantly altered drug transporter expression in liver and kidney, which corresponded with urinary APAP metabolite levels.

An innovative adsorption/nitrification/denitrification/sludge-hydrolysis wastewater treatment process (ENRS) characterized by carbon source manipulation with a biological adsorption unit and a sludge hydrolysis unit was developed to enhance nitrogen removal and reduce sludge production for municipal wastewater treatment. The system presented good performance in pollutants removal, yielding the effluent with average COD, NH(4)(+)-N, TN and TP of 48.5, 0.6, 13.2 and 1.0mg/L, respectively. Sixty percent of the total carbon source in the influent was concentrated and separated by the quick adsorption of activated sludge, providing the possibilities of reusing waste carbon source in the denitrification tank and accumulating nitrobacteria in the nitrification tank. Low temperature of 6-15°C and high hydraulic loading rate of 3.0-15.0m(3)/d did not affect NH(4)(+)-N removal performance, yielding the NH(4)(+)-N of lower 1.0mg/L in the effluent. Furthermore, 50% of the residual sludge in the ENRS system could be transformed into soluble COD (SCOD) by alkaline thermal hydrolysis with temperature of 60°C and pH of 11, and the hydrolyzed carbon could completely substitute methanol as a good quality carbon to support high efficient denitrification.

The caspase family is well characterized as playing a crucial role in modulation of programmed cell death (PCD), which is a genetically regulated, evolutionarily conserved process with numerous links to many human diseases, most notably cancer. In this review, we focus on summarizing the intricate relationships between some members of the caspase family and their key apoptotic mediators, involving tumour necrosis factor receptors, the Bcl-2 family, cytochrome c, Apaf-1 and IAPs in cancer initiation and progression. We elucidate new emerging types of cross-talk between several caspases and autophagy-related genes (Atgs) in cancer. Moreover, we focus on presenting several PCD-modulating agents that may target caspases-3,-8 and -9, and their substrates PARP-1 and Beclin-1, which may help us harness caspase-modulated PCD pathways for future drug discovery.

The articular cartilage collagen network is an important research focus because network disruption results in cartilage degeneration and patient disability. The recently introduced helium ion microscope (HIM), with its smaller probe size, longer depth of field and charge neutralization, has the potential to overcome the inherent limitations of electron microscopy for visualization of collagen network features, particularly at the nanoscale. In this study, we evaluated the capabilities of the helium ion microscope for high-resolution visualization of the articular cartilage collagen network. Images of rabbit knee cartilage were acquired with a helium ion microscope; comparison images were acquired with a field emission scanning electron microscope (FE-SEM) and a transmission electron microscope (TEM). Sharpness of example high-resolution helium ion microscope and field emission scanning electron microscope images was quantified using the 25-75% rise distance metric. The helium ion microscope was able to acquire high-resolution images with unprecedented clarity, with greater sharpness and three-dimensional-like detail of nanoscale fibril morphologies and fibril connections, in samples without conductive coatings. These nanoscale features could not be resolved by field emission scanning electron microscopy, and three-dimensional network structure could not be visualized with transmission electron microscopy. The nanoscale three-dimensional-like visualization capabilities of the helium ion microscope will enable new avenues of investigation in cartilage collagen network research.

Michelia maudiae Dunn. is a Magnoliaceae species threatened by habitat destruction and over-exploitation. Genetic diversity and differentiation, population contribution to total diversity and allelic/haplotypic richness, and the relative importance of pollen- and seed-mediated gene flow were investigated in nine populations (192 individuals) of M. maudiae using nuclear and chloroplast microsatellites to further our understanding of the genetic structure and evolutionary history of this tree species and to provide a genetic perspective for its conservation. The species had strong pollen mediated gene flow in the past. The ratio of pollen to seed gene flow was 25.4. Three clusters from the western, central, and eastern China were identified by both chloroplast and nuclear microsatellites. Western populations at Xiaodanjiang and Daoxian were phylogenetically divergent from the remaining populations and might be particularly important for the conservation of this species. The populations of Xiaodanjiang, Daoxian, and Minjiangyuan made positive contribution to the total diversity and allelic/haplotypic richness, and were worthy of being conserved with priority. In the central cluster, population at Laopengding should be protected since it harbored the greatest genetic diversity.

Although recent researches show that Heat Shock Protein 72 (HSP72) plays an important role in neuronal survival, little knowledge is known about the precise mechanisms during cerebral ischemia/reperfusion (I/R). Our present study investigated the neuroprotective mechanisms of HSP72 against ischemic brain injury induced by cerebral I/R. Mild heat shock pretreatment was employed to induce the overexpression of HSP72 by immersing rats into the water bath at 42°C for 20min before cerebral I/R. HSP72 antisense oligodeoxynucleotides (ODNs) were used to inhibit HSP72 expression by intracerebroventricular infusion once per day for 3days before cerebral I/R animal model was induced by four-vessel occlusion for 15min transient ischemia and then reperfused for various time in Sprague-Dawley rats. Immunoprecipitation and immunoblotting were used to detect the expression of the related proteins. HE-staining and TUNEL-staining were carried out to examine the neuronal death of hippocampal CA1 region. Results showed that mild heat shock could increase the phosphorylation of protein kinase B (Akt), inhibit the assembly of MLK3-MKK7-JNK3 signaling module, diminish the phosphorylation of JNK3 and c-Jun, and decrease the activation of caspase-3. Furthermore, mild heat shock could significantly protect neurons against cerebral I/R. Whereas, all of the aforementioned effects of mild heat shock were reversed by HSP72 antisense ODNs. In summary, our results imply that Akt1 activation is involved in the neuroprotection of HSP72 against ischemic brain injury via suppressing JNK3 signaling pathway and provide a new experimental foundation for stroke therapy.

PURPOSE: Sevoflurane is used widely during lung cancer surgery. However, the effect of sevoflurane on the invasion and migration of lung carcinoma cells remains unclear. The aims of this study were to explore the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the effect of sevofluane on the invasion and the role of fascin and ezrin on the effect of sevofluane on the migration of human lung adenocarcinoma A549 cells. We also investigated whether sevoflurane regulates the expression of these molecules through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. METHODS: The invasion of cells was evaluated using the Transwell invasion assay, and the migration of cells was determined using the wound healing assay. The expression of MMP-2, MMP-9, ezrin, fascin, and phospho-p38 MAPK in cells was determined by western blotting. RESULTS: A significant inhibition of cell invasion and migration was found in A549 cells which had been treated with sevoflurane. The data also revealed that sevoflurane could decrease the phosphorylation level of p38 MAPK, which is involved in the downregulation of MMP-2, MMP-9, fascin, and ezrin expression, accompanied by a concomitant inhibition of the invasion and migration of A549 cells. SB203580, a p38 MAPK inhibitor, augmented the downregulation of the expression of these proteins. CONCLUSION: The anti-invasion effect of sevoflurane on A549 cells was associated with a downregulation of both MMP-2 and MMP-9 expression, while the anti-migration effect was associated with a downregulation of both fascin and ezrin expression. These effects could occur partly as a result of inactivation of the p38 MAPK signaling pathway.