Fixing the Broken Phosphorus Cycle: Wastewater Remediation by Microalgal Polyphosphates

Phosphorus (P), in the form of phosphate derived from either inorganic (Pi) or organic (Po) forms is an essential macronutrient for all life. P undergoes a biogeochemical cycle within the environment, but anthropogenic redistribution through inefficient agricultural practice and inadequate nutrient recovery at wastewater treatment works have resulted in a sustained transfer of P from rock deposits to land and aquatic environments. Our present and near future supply of P is primarily mined from rock P reserves in a limited number of geographical regions. To help ensure that this resource is adequate for humanity’s food security, an energy-efficient means of recovering P from waste and recycling it for agriculture is required. This will also help to address excess discharge to water bodies and the resulting eutrophication. Microalgae possess the advantage of polymeric inorganic polyphosphate (PolyP) storage which can potentially operate simultaneously with remediation of waste nitrogen and phosphorus streams and flue gases (CO2, SOx, and NOx). Having high productivity in photoautotrophic, mixotrophic or heterotrophic growth modes, they can be harnessed in wastewater remediation strategies for biofuel production either directly (biodiesel) or in conjunction with anaerobic digestion (biogas) or dark fermentation (biohydrogen). Regulation of algal P uptake, storage, and mobilization is intertwined with the cellular status of other macronutrients (e.g., nitrogen and sulphur) in addition to the manufacture of other storage products (e.g., carbohydrate and lipids) or macromolecules (e.g., cell wall). A greater understanding of controlling factors in this complex interaction is required to facilitate and improve P control, recovery, and reuse from waste streams. The best understood algal genetic model is Chlamydomonas reinhardtii in terms of utility and shared resources. It also displays mixotrophic growth and advantageously, species of this genus are often found growing in wastewater treatment plants. In this review, we focus primarily on the molecular and genetic aspects of PolyP production or turnover and place this knowledge in the context of wastewater remediation and highlight developments and challenges in this field

A phase II trial of ixabepilone in Asian patients with advanced gastric cancer previously treated with fluoropyrimidine-based chemotherapy

PURPOSE: The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, but no single standard of care exists following disease progression. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical activity across multiple tumor types approved by the United States Food and Drug Administration for treatment of metastatic breast cancer. METHODS: Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m(2) by 3-h intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR). RESULTS: Fifty-two patients were treated (65.4 % men; median age: 56.5 years). The ORR was 15.4 % (95 % confidence interval [CI] 6.9-28.1); 8 patients achieved partial responses for a median duration of 3.1 months (95 % CI 2.6-4.1 months) and 26 patients (50.0 %) had stable disease. Median progression-free survival was 2.8 months (95 % CI 2.1-3.5 months). The most common grade 3 non-hematological toxicities were fatigue (9.6 %), decreased appetite (7.7 %), sensory neuropathy (5.8 %), and diarrhea (5.8 %). Grade 3/4 neutropenia occurred in 46.2 % of patients. CONCLUSIONS: Ixabepilone is active in Asian patients with advanced gastric cancer and shows a toxicity profile similar to those previously reported in other tumor types.published_or_final_versio

Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

Research Fund for the Control of Infectious Diseases: Research Dissemination Reports (Series 2)1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.published_or_final_versio

Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection.

Key Messages 1. Severe acute respiratory syndrome (SARS) patients who are homozygous for intercellular adhesion molecule-3 (ICAM-3) Gly143 showed significant association with higher lactate dehydrogenase levels and lower total white blood cell counts on admission. 2. In vitro functional studies demonstrated low level binding of ICAM-3 to DC-SIGN and a wide variation in T-cell response of the wild-type ICAM-3 genotype.published_or_final_versio

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Association of a single nucleotide polymorphism in the CD209 (DC-SIGN) promoter with SARS severity.

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Therapeutic potential of TLR8 agonist GS-9688 (selgantolimod) in chronic hepatitis B: re-modelling of antiviral and regulatory mediators

Background & Aims: GS‐9688 (selgantolimod) is a toll‐like receptor 8 (TLR8) agonist in clinical development for the treatment of chronic hepatitis B (CHB). Antiviral activity of GS‐9688 has previously been evaluated in vitro in hepatitis B virus (HBV)‐infected hepatocytes and in vivo in the woodchuck model of CHB. Here we evaluated the potential of GS‐9688 to boost responses contributing to viral control and to modulate regulatory mediators. Approach & Results: We characterised the effect of GS‐9688 on immune cell subsets in vitro in PBMC of healthy controls and CHB patients. GS‐9688 activated dendritic cells and mononuclear phagocytes to produce IL‐12 and other immunomodulatory mediators, inducing a comparable cytokine profile in healthy controls and CHB patients. GS‐9688 increased the frequency of activated natural killer (NK) cells, mucosal‐associated invariant T‐cells (MAITs), CD4+ follicular helper T‐cells (TFH) and, in ~50% of patients, HBV‐specific CD8+T‐cells expressing interferon‐γ (IFNγ). Moreover, in vitro stimulation with GS‐9688 induced NK cell expression of IFNγ and TNFα and promoted hepatocyte lysis. We also assessed whether GS‐9688 inhibited immunosuppressive cell subsets that might enhance antiviral efficacy. Stimulation with GS‐9688 reduced the frequency of CD4+ regulatory T‐cells and monocytic myeloid‐derived suppressor cells (MDSC). Residual MDSC expressed higher levels of negative immune regulators, galectin‐9 and PD‐L1. Conversely, GS‐9688 induced an expansion of immunoregulatory TNF‐related apoptosis‐inducing ligand+ (TRAIL) regulatory NK cells and degranulation of arginase‐I+ polymorphonuclear‐MDSC (PMN‐MDSC). Conclusions: GS‐9688 induces cytokines in human PBMC that are able to activate antiviral effector function by multiple immune mediators (HBV‐specific CD8+T‐cells, TFH, NK cells and MAITs). Whilst reducing the frequency of some immunoregulatory subsets, it enhances the immunosuppressive potential of others, highlighting potential biomarkers and immunotherapeutic targets to optimise the antiviral efficacy of GS‐9688

CT scanning for diagnosing blunt ureteral and ureteropelvic junction injuries

<p>Abstract</p> <p>Background</p> <p>Blunt ureteral and ureteropelvic (UPJ) injuries are extremely rare and very difficult to diagnose. Many of these injuries are missed by the initial trauma evaluation.</p> <p>Methods</p> <p>Trauma registry data was used to identify all blunt trauma patients with ureteral or UPJ injuries, from 1 April 2001 to 30 November 2006. Demographics, injury information and outcomes were determined. Chart review was then performed to record initial clinical and all CT findings.</p> <p>Results</p> <p>Eight patients had ureteral or UPJ injuries. Subtle findings such as perinephric stranding and hematomas, and low density retroperitoneal fluid were evident on all initial scans, and prompted delayed excretory scans in 7/8 cases. As a result, ureteral and UPJ injuries were diagnosed immediately for these seven patients. These findings were initially missed in the eighth patient because significant associated visceral findings mandated emergency laparotomy. All ureteral and UPJ injuries have completely healed except for the case with the delay in diagnosis.</p> <p>Conclusion</p> <p>Most blunt ureteral and UPJ injuries can be identified if delayed excretory CT scans are performed based on initial CT findings of perinephric stranding and hematomas, or the finding of low density retroperitoneal fluid.</p

The effect of silver fluoride and potassium iodide on the bond strength of auto cure glass ionomer cement to dentine

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been shown to reduce the incidence of caries in primary dentitions. The clinical application of this material has been limited by staining associated with both teeth and restorative materials. The application of potassium iodide (KI) after AgF eliminates stain formation. There is a lack of information as to how the addition of AgF followed by KI may affect the bond strength to dentine. The purpose of this study was to compare the bond strengths of auto cure glass ionomer cement to dentine surfaces that had been treated with AgF and KI and without treatment. Methods: Ten recently extracted human third molars were embedded into methyl methacrylate resin and sliced to form a square block of exposed dentine surfaces. Each of the four surfaces were treated by one of the following procedures: (a) etching with 37 per cent phosphoric acid; (b) applying GC dentine conditioner; (c) etching, followed by application of AgF/KI then washing off the precipitate and air drying; and (d) etching, applying AgF/KI and air drying the reaction products on the surface. Fuji VII auto cure glass ionomer cement was bonded onto each sample and fracture tested. Results: The dentine samples treated with AgF/KI followed by washing away the precipitate and air drying had bond strengths (2.83MPa) not significantly different from samples that had been conditioned (2.40MPa). Samples where the AgF/KI precipitate had been air dried onto the dentine surface had significantly lower bond strengths (1.49MPa) than the washed samples. Samples that were etched had significantly lower bond strengths (1.91MPa) than the conditioned samples. Conclusions: This study found that the application of AgF/KI to etched dentine samples followed by washing off the precipitate, created bond strengths that were not significantly different to conditioned samples. Leaving the AgF/KI precipitate on the dentine surface significantly reduced the bond strength of auto cured glass ionomer cement to dentine. Washing away the reaction products and air drying is recommended as the clinical protocol for using AgF and KI on dentine surfaces prior to application of an auto cure glass ionomer cement.GM Knight, JM McIntyre, Mulyan

Characterization of the Psychological, Physiological and EEG Profile of Acute Betel Quid Intoxication in Naïve Subjects

Betel quid use and abuse is wide spread in Asia but the physiological basis of intoxication and addiction are unknown. In subjects naïve to the habit of betel quid intoxication, the psychological and physiological profile of intoxication has never been reported. We compared the effect of chewing gum or chewing betel quid, and subsequent betel quid intoxication, on psychological assessment, prospective time interval estimation, numerical and character digit span, computerized 2 choice tests and mental tasks such as reading and mathematics with concurrent monitoring of ECG, EEG and face temperature in healthy, non-sleep deprived, male subjects naïve to the habit of chewing betel quid. Betel quid intoxication, dose dependently induced tachycardia (max 30 bpm) and elevated face temperature (0.7°C) (P<0.001) above the effects observed in response to chewing gum (max 12 bpm and 0.3°C) in 12 subjects. Gross behavioral indices of working memory such as numerical or character digit span in 8 subjects, or simple visual-motor performance such as reaction speed or accuracy in a two choice scenario in 8 subjects were not affected by betel quid intoxication. Betel quid intoxication strongly influenced the psychological aspects of perception such as slowing of the prospective perception of passage of a 1 minute time interval in 8 subjects (P<0.05) and perceived increased arousal (P<0.01) and perceived decreased ability to think (P<0.05) in 31 subjects. The EEG spectral profile recorded from mental states associated with open and closed eyes, and mental tasks such as reading and eyes closed mental arithmetic were significantly modified (P<0.05) relative to chewing gum by betel quid intoxication in 10 subjects. The prevalence of betel quid consumption across a range of social and work settings warrants greater investigation of this widespread but largely under researched drug