Potential Therapeutic Relevance of CRISPR/Cas9 Guided Epigenetic Regulations for Neuropsychiatric Disorders.

Brain function activity is regulated by several mechanisms of genetic and epigenetic factors such as histone modelling, DNA methylation, and non-coding RNA. Alterations in these regulatory mechanisms affect the normal development of neurons that causes Neuropsychiatric Disorders (ND). However, it is required to analyse the functional significance of neuropsychiatric disorders associated with a molecular mechanism to bring about therapeutic advances in early diagnosis and treatment of the patients. The CRISPR/Cas 9 (Clustered Regularly Interspaced Short Palindromic Repeats) genome editing tools have revolutionized multiple genome and epigenome manipulation targets the same time. This review discussed the possibilities of using CRISPR/Cas 9 tools during molecular mechanism in the ND as a therapeutic approach to overcome ND that is caused due to genetic and epigenetic abnormalities.

Solubilized delivery of paliperidone palmitate by D-alpha-tocopheryl polyethylene glycol 1000 succinate micelles for improved short-term psychotic management.

The objective of this work was to formulate paliperidone palmitate-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for improved antipsychotic effect during short-term management of psychotic disorders. Vitamin E TPGS micelles containing paliperidone palmitate were prepared by the solvent casting method and control paliperidone palmitate formulations were prepared by simple sonication method. The prepared micelles and control paliperidone palmitate formulations were evaluated for different parameters. Particle sizes of prepared micelles, control paliperidone palmitate formulations were determined at 25 °C by dynamic light scattering technique and external surface morphology was determined by transmission electron microscopy analysis. The encapsulation efficiency was determined by spectrophotometery. In-vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the paliperidone palmitate-loaded TPGS micelles were 26.5 nm. About 92% of drug encapsulation efficiency was achieved with micelles. The drug release from paliperidone palmitate-loaded TPGS micelles was sustained for more than 24 h with 40% of drug release. The TPGS product, i.e. paliperidone palmitate-loaded micelles, resulted in nano-sized delivery, solubility enhancement and permeability of the micelles which provided an improved and prolonged anti-psychotic effect in comparison to control paliperidone palmitate formulation.

Anaerobic co-digestion of microalgae Chlorella sp. and waste activated sludge.

The study investigated the growth characteristics of environmental algal strain, Chlorella, in the modified Zarrouk medium and its anaerobic co-digestion with waste activated sludge (WAS). Analysis of extracellular polymeric substances (EPS) in algal culture and WAS indicated that Chlorella secreted more EPS into the surrounding liquid than formed floc-associated EPS as in activated sludge. Mesophilic anaerobic digestion of algae alone required extended digestion period to produce methane, with biogas yield at 262 mL/gVSfed after 45 days of digestion. When algae was co-digested with varying amounts of WAS, 59-96% in mass, not only biogas yield of microalgae improved but the gas phase was reached more quickly. The dewaterability of co-digestion products were also better than two controls digesting WAS or algae only. These results suggest that anaerobic co-digestion of algae and sludge improves the digestibility of microalgae and could also bring synergistic effects on the dewaterability of digested products for existing anaerobic digesters.

Utilisation of wastewater nutrients for microalgae growth for anaerobic co-digestion.

The feasibility of growing microalgae in natural light using wastewater high in nutrients (N & P) for the production of more bioenergy was examined. The main retrofitting unit would be a photobioreactor for wastewater treatment plants (wwtp) having anaerobic digesters in close proximity. Theoretical microalgae production rates from different wastewater sources (municipal wwtp, source separation of human and animal wastewaters) were estimated using mass balance. Mass and energy balances for a conventional wwtp using chemically enhanced primary treatment was investigated for microalgae growth for a situation limited by availability of carbon dioxide (CO2) generated onsite and where additional CO2 was imported from outside source. Reject water from dewatering of anaerobically digested sludge from four wwtp around Oslo region were pretreated for improved light penetration and examined for microalgae growth. Several pre-treatment methods were investigated. Pretreatment using flocculation + settling + anthracite filtration yielded high light transmittance. A maximum microalgae growth rate of 13 g TSS/m(2)-d was achieved using this pretreated reject water. The challenges of integrating photobioreactors with existing units have been highlighted.

Microalgae growth using high-strength wastewater followed by anaerobic co-digestion.

Integration of algal biofuel production to wastewater anaerobic digestion infrastructure has the potential to increase biogas production, decrease high and variable internal nitrogen loads, and improve sludge digestibility and dewaterability. In this research, two species of microalgae, Spirulina platensis and Chlorella sp., were grown on sludge centrate and a centrate and nitrified wastewater effluent mixture. Harvested algae were co-digested with waste activated sludge (WAS) at varying ratios. High-growth (6.8 g m(-2) x d(-1)), nitrogen (36.5 g m(-3) x d(-1)), and phosphorus (6.5 g m(-3) x d(-1)) uptake rates were achieved with Chlorella on centrate. No growth was observed with S. platensis under the same conditions; however, both organisms grew well on the centrate and effluent mixture. Co-digestion of algae with WAS improved volatile solids reduction. Although co-digestion with S. platensis improved biosolids dewaterability, Chlorella had a slight negative effect on dewaterability compared to WAS alone. The efficiency of energy conversion from photons to biogas generated from Chlorella was estimated at 1.4%.

Impact of ammonia concentration on Spirulina platensis growth in an airlift photobioreactor.

Spirulina platensis was cultivated in a bench-scale airlift photobioreactor using synthetic wastewater (total nitrogen 412 mg L(-1), total phosphorous 90 mg L(-1), pH 9-10) with varying ammonia/total nitrogen ratios (50-100% ammonia with balance nitrate) and hydraulic residence times (15-25 d). High average biomass density (3500-3800 mg L(-1)) and productivity (5.1 g m(-2) d(-1)) were achieved when ammonia was maintained at 50% of the total nitrogen. Both high ammonia concentrations and mutual self-shading, which resulted from the high biomass density in the airlift reactor, were found to partially inhibit the growth of S. platensis. The performance of the airlift bioreactor used in this study compared favorably with other published studies. The system has good potential for treatment of high strength wastewater combined with production of algae for biofuels or other products, such as human and animal food, food supplements or pharmaceuticals.

Microalgae growth for nutrient recovery from sludge liquor and production of renewable bioenergy.

Proof-of-concept has been demonstrated for a process that will utilize nutrients from sludge liquor, natural light, and CO2 from biogas to grow microalgae at wastewater treatment plants. This process will reduce the impact of returning side-streams to the head of the plant. The produced algae will be fed to anaerobic digesters for increased biogas production. Dewatering of anaerobically digested sludge in centrifuges produces reject water with extremely low transmittance of light. A pretreatment procedure was developed that improved light transmittance for reject water from the FREVAR, Norway, wastewater treatment plant from 0.1% T to 77% T (670 nm, 1 cm path). Chlorella sp. microalgae were found to be suitable for growth in this pre-treated reject water. Typical nitrogen removal was 80-90 g N/kg TSS of produced microalgae. The microalgae were successfully harvested by chemically assisted flocculation followed by straining through a 33 microm sieve cloth, achieving up to 99% recovery. Harvested algae were anaerobically co-digested with wastewater sludge. The specific methane gas production (mL CH4/g VS fed) for the algae varied from less than 65% to 90% of the specific methane gas production for the wastewater sludge, depending on digester temperature, retention time and pre-treatment of the algae biomass.

Enhanced CO(2) fixation and biofuel production via microalgae: recent developments and future directions.

Unbalanced production of atmospheric CO(2) constitutes a major challenge to global sustainability. Technologies have thus been developed for enhanced biological carbon fixation (also referred to as CO(2) mitigation), and one of the most promising capitalizes on microalgae. However, the "best bioreactor", which would be able to achieve maximum productivity and maximum energy efficiency under a given set of operational costs, does not exist. This review briefly examines the current technologies available for enhanced microalgal CO(2) fixation, and specifically explores the possibility of coupling wastewater treatment with microalgal growth for eventual production of biofuels and/or added-value products, with an emphasis on productivity. In addition, an overview of reactor configurations for CO(2) fixation and bottlenecks associated with the underlying technology are provided. Finally, a review of life cycle analysis studies is presented, and routes for improvement of existing processes are suggested.

Onsite wastewater denitrification using a hydrogenotrophic hollow-fiber membrane bioreactor.

Hydrogenotrophic wastewater denitrification was investigated using a bench-scale hollow-fiber membrane bioreactor (HFMB). In the HFMB, hydrogen (H2) was passed through the lumen of hollow-fiber membranes and nitrified wastewater was supplied to the shell of the reactor. A mass transfer model was developed and found to be a good tool to estimate H2 mass transfer coefficients at varying recirculation velocities. Under steady conditions, effluent NO3(-)-N concentrations less than 10 mg/L were achieved at an empty bed contact time of 8.3 hours when pH and membrane fouling were controlled. An average nitrogen flux of 0.88 g NO3(-) -N/m2 x d was observed. Dissolved oxygen in the influent wastewater did not adversely affect overall nitrogen removal. Under transient conditions, similar to those of onsite processes, overall nitrogen removal efficiencies of 74 to 82% were observed. Confocal laser scanning microscopy revealed that the denitrifying biofilm was loosely associated with the membrane surfaces.

Biological perchlorate reduction in packed bed reactors using elemental sulfur.

Sulfur-utilizing perchlorate (ClO4-)-reducing bacteria were enriched from a denitrifying wastewater seed with elemental sulfur (S0) as an electron donor. The enrichment was composed of a diverse microbial community, with the majority identified as members of the phylum Proteobacteria. Cultures were inoculated into bench-scale packed bed reactors (PBR) with S0 and crushed oyster shell packing media. High ClO4-concentrations (5-8 mg/L) were reduced to < 0.5 mg/L at an empty bed contact time (EBCT) of 13 h. Low C1O4- concentrations (60-120 microg/L), more typical of contaminated groundwater sites, were reduced to < 4 microg/L at an EBCT of 7.5 h. PBR performance decreased when effluent recirculation was applied or when smaller S0 particle sizes were used, indicating that mass transfer of ClO4- to the attached biofilm was not the limiting mechanism in this process, and that biofilm acclimation and growth were key factors in overall reactor performance. The presence of nitrate (6.5 mg N/L) inhibited ClO4- reduction. The microbial community composition was found to change with ClO4- availability from a majority of Beta-Proteobacteria near the influent end of the reactor to primarily sulfur-oxidizing bacteria near the effluent end of the reactor.

Hydrogenotrophic denitrification and perchlorate reduction in ion exchange brines using membrane biofilm reactors.

Halophilic (salt loving), hydrogenotrophic (H(2) oxidizing) denitrifying bacteria were investigated for treatment of nitrate (NO3-) and perchlorate (ClO4-) contaminated groundwater and ion exchange (IX) brines. Hydrogenotrophic denitrifying bacteria were enriched from a denitrifying wastewater seed under both halophilc and non-halophilc conditions. The cultures were inoculated into bench-scale membrane biofilm reactors (MBfRs) with an "outside in" configuration, with contaminated water supplied to the lumen of the membranes and H(2) supplied to the shell. Abiotic mass transfer tests showed that H(2) mass transfer coefficients were lower in brines than in tap water at highest Reynolds number, possibly due to increased transport of salts and decreased H(2) solubility at the membrane/liquid interface. An average NO3- removal efficiency of 93% was observed for the MBfR operated in continuous flow mode with synthetic contaminated groundwater. Removal efficiencies of 30% for NO3- and 42% for ClO4- were observed for the MBfR operated with synthetic IX brine in batch operating mode with a reaction time of 53 h. Phylogenetic analysis focused on the active microbial community and revealed that halotolerant, NO3- -reducing bacteria of the bacterial classes Gamma-Proteobacteria and Sphingobacteria were the metabolically dominant members within the stabilized biofilm. This study shows that, despite decreased H(2) transfer under high salt conditions, hydrogenotrophic biological reduction may be successfully used for the treatment of NO3- and ClO- in a MBfR.