Cholesterol metabolism is altered in Rett syndrome: A study on plasma and primary cultured fibroblasts derived from patients

Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology

TREATMENT OF LANDFILL LEACHATE IN SBR SYSTEMS: ANALYSIS OF BIOMASS ACTIVITY BY MEANS OF RESPIROMETRIC TECHNIQUES

In the last decades landfilling has been the main method of municipal solid waste (MSW) disposal in many countries. MSW landfills are usually considered as a large biological reactor where the MSWs undergo anaerobic digestion producing gas and liquid emissions. Aged, or mature leachate, which is produced by older landfills, can be very refractory; for this reason mature leachate is difficult to treat alone, but it can be co-treated with sewage or domestic wastewater. The aim of the study was to investigate the feasibility of co-treatment of landfill leachate and synthetic wastewater in different percentages, in terms of process performance and biomass activity, by means of respirometric techniques. Two sequencing batch reactors (SBR) were fed with synthetic wastewater and different percentages of landfill leachate (respectively 10% and 50% V/V in SBR1 and SBR2). The obtained results showed a good organic carbon removal efficiency for both reactors; ammonia removal efficiency showed different trends between SBR1 and SBR2, probably due to inhibition factors exerted by high landfill leachate percentage present in SBR2

Carbon and nutrient biological removal in a University of Cape Town membrane bioreactor: Analysis of a pilot plant operated under two different C/N ratios

The effect of the carbon-to-nitrogen (C/N) ratio variation in a University of Cape Town Membrane bioreactor (UCT-MBR) was investigated. The experimental campaign was divided into two phases, each characterized by a different C/N ratio (namely, 10 and 5, Phase I and Phase II, respectively). The UCT-MBR pilot plant was analysed in terms of carbon and nutrients removal, biomass respiratory activity, activated sludge features and membrane fouling. The results highlighted that the nutrients removal was significantly affected by the decrease of the C/N ratio during the Phase II. The biological carbon removal was also affected by the low C/N value during the Phase II. Indeed, the average biological COD removal efficiency was equal to 72.9% during the Phase II, while the average value was 82.8% in the Phase I. The respirometric batch test suggested that both heterotrophic and autotrophic species were severely affected by the lower C/N ratio in the Phase II. Moreover, a decrease of the membrane filtration properties was observed during the Phase II, mainly due to the worsening of the activated sludge features, which enhanced the increase of SMP production

Towards a conceptual mathematical tool linking physical and biological processes for a reduction of ghg emissions from an mb-mbr plant

The current study explores the influence of the air flow rate on greenhouse gas (GHG) emissions (direct and indirect), the operational costs (OCs), the effluent quality index (EQI) and effluent fines (EF). An University Cape Town (UCT) moving bed (MB) membrane bioreactor (MBR) pilot plant has been considered as case study where the influence of the air flow rate on the biological and physical processes has been analyzed. Constitutive relationships between the air flow rate and some performance indicators (i.e., EQI, OCs, direct and indirect GHG emissions) have been identified. Results showed that the EQI increases at low flow rate likely due to the dissolved oxygen (DO) limitation in the biological processes. Direct GHGs are influenced by air flow exponentially increasing with the increase of the air flow due to the anoxic N2O contribution. Irreversible membrane fouling reduce from 98% to 85% with the increasing of the air flow rate from 0.57 m3 h-1 to 2.56 m3 h- 1. However, the increase of the air flow rate leads to the increase of the N2O-N flux emitted from the MBR (from 40% to 80%). In order to establish a mathematical tool to reduce GHG emissions maintaining good effluent quality, results suggest of adopting a relationship based on a “multiple objective”

Nitrous oxide emission from a moving bed membrane biofilm reactor: the effect of the sludge retention time

The aim of the present study was to investigate the nitrous oxide (N2O) emissions from a University of Cape Town (UCT) moving bed membrane bioreactor pilot plant. An experimental campaign was carried out during 60 days with three different sludge retention time (SRT). The pilot plant reactor was provided of funnel shape covers that guaranteed gas accumulation in the headspace. The results highlighted that N2O concentrations significantly increased when the biofilm concentrations increased within the aerobic and anoxic compartments. Furthermore, results have shown an increase of N2O with the decrease of SRT. Moreover, the MBR tank resulted the key emission source (up to 70% of the total N2O emission during SRT=∞ period) whereas the highest N2O production occurred in the anoxic reactor. Moreover, N2O concentrations measured in the permeate flow were not negligible, thus highlighting its potential detrimental contribution for the receiving water body

Removal of carbon and nutrients from wastewater in a moving bed membrane biofilm reactor: the influence of the sludge retention time

A University of Cape Town (UCT) pilot plant combining both membrane bioreactor (MBR) and moving bed biofilm reactor (MBBR) technology was monitored. Three experimental Phases were carried out by varying the mixed liquor sludge retention time (SRT) (indefinite, 30 and 15 days, respectively). The system performance has been investigated during experiments in terms of: organic carbon, nitrogen and phosphorus removal, biokinetic/stoichiometric constants, membrane fouling tendency and sludge dewaterability. The observed results showed that by decreasing the SRT the UCT pilot plant was able to maintain very high total COD removal efficiencies, whilst the biological COD removal efficiency showed a slight decrease. Nitrification was only slightly affected by the decrease of the mixed liquor SRT, showing high performance (as average). This result could be related to the presence of the biofilm able to sustain nitrification throughout experiments. Conversely, the average P removal efficiency was quite moderate, likely due to the increase of the ammonium loading rate that could promote an increased NO3-N recycled from the anoxic to the anaerobic tank, interfering with phosphorus accumulating organisms (PAOs) activity inside the anaerobic tank. Membrane fouling increased at 30 days SRT likely due to a reduction of protective cake pre-filter effect. Moreover, it was noticed the increase of the resistance due to pore blocking and a general worsening of the membrane filtration properties

Speckle-based imaging (SBI) applications with spectral photon counting detectors at the newly established OPTIMATO (OPTimal IMAging and TOmography) laboratory

Speckle-based imaging (SBI) is an advanced X-ray imaging technique that measures phase and dark-field signals, in addition to absorption signals. SBI uses random wavefront modulators to generate speckles and requires two images: one with a speckle pattern alone, and one with both the sample and speckles. SBI reconstruction algorithms retrieve three signals (transmission, refraction, and dark-field) by comparing the two images. In SBI, speckle visibility plays a crucial role in the retrieval of the three signals. When translating the technique from synchrotron sources to compact laboratory setups, the reduced coherence of the source and limitations in the available resolution yield lower speckle visibility, hampering the retrieval of phase and dark-field signals. In this context, direct-detection CdTe X-ray photon-counting detectors (XPCDs) provide an attractive solution, as they allow for a high detection efficiency and optimal spatial resolution enhancing speckle visibility. In this work, we present the newly established OPTIMATO (OPTimal IMAging and TOmography) laboratory for X-ray imaging hosted at the Elettra synchrotron (Trieste, Italy). The setup for SBI with resolutions up to 15 μm including an XPCD and a charge-integrating flat-panel detector (FPD) has been used to acquire SBI data. The main limiting factors when moving SBI applications from synchrotron facilities to compact laboratory setups are summarized. The advantages of XPCDs over FPDs are discussed by comparing the SBI images obtained using both detectors. The potential of the spectral decomposition approach via multi-threshold acquisitions using XPCDs is briefly introduced. The results shown in this work represent the first step toward the realization of a multimodal and multiresolution X-ray facility

High-speed processing of X-ray wavefront marking data with the Unified Modulated Pattern Analysis (UMPA) model

Wavefront-marking X-ray imaging techniques use e.g., sandpaper or a grating to generate intensity fluctuations, and analyze their distortion by the sample in order to retrieve attenuation, phase-contrast, and dark-field information. Phase contrast yields an improved visibility of soft-tissue specimens, while dark-field reveals small-angle scatter from sub-resolution structures. Both have found many biomedical and engineering applications. The previously developed Unified Modulated Pattern Analysis (UMPA) model extracts these modalities from wavefront-marking data. We here present a new UMPA implementation, capable of rapidly processing large datasets and featuring capabilities to greatly extend the field of view. We also discuss possible artifacts and additional new features.Comment: 18 pages, 7 figures, submitted to Optics Expres