SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells

Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells.     

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the contribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents.     

Adsorption of Pb and Cd in rice husk and their immobilization in porous glass-ceramic structures

Rice husk, an agricultural waste, is abundantly available in many countries such as China, India, Brazil, US, and South East Asia. Despite the massive production of rice husk, it is mainly disposed to landfill. In this work, utilization of rice husk for a potential waste-water treatment is evaluated, along with subsequent encapsulation of the adsorbed heavy metals (Pb and Cd) inside a porous glass-ceramic. Vitrified bottom ash (another source of waste) was mixed with foaming agents in dif- ferent weight ratios (40:60, 50:50, and 60:40) to prepare a glass matrix for encapsulation of Pb-/Cd-loaded rice husk. It was shown that using 40 wt% vitrified bottom ash with 60 wt% foaming agents leads to a foam glass with the best pore size distribution. Therefore, this batch was further mixed with 70 volume% (5 wt%) heavy metal-loaded rice husk and was heat-treated at 750°C for 3 hours. The final glass-ceramic porous structure was char acterized using SEM, XRD, compression test, and it was shown that it is safe to be used as it passes the EN12457-2 leaching test.     

Enhanced microbial oil production by activated sludge microorganisms via co‐fermentation of glucose and xylose

The co‐fermentation of glucose and xylose by activated sludge microorganisms for the production of microbial oils for use as biodiesel feedstock was investigated. Various carbon sources at initial concentration of 60 g/L and C:N ratio 70:1 were investigated: xylose, glucose, and 2:1 and 1:2 (by mass) glucose/xylose mixtures. Oil accumulation ranged between 12 to 22% CDW, the highest of which was obtained when xylose was the sole substrate used. Kinetic modeling of the fermentation data showed that specific growth and oil accumulation rates were similar in all substrate types and the lipid coefficient ranged from 0.02 to 0.06 g/g of sugar consumed. The fatty acid methyl ester yield and composition of the lipids showed their suitability for conversion to biodiesel. Based on the results, lignocellulose sugars could be used as fermentation substrates by activated sludge microorganisms for enhancing the oil content of sewage sludge for its use as a sustainable biofuel feedstock source. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4036–4044, 2013     

Antioxidant properties,radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study

BACKGROUND: This study was designed to evaluate and compare antioxidant capacity and radical scavenging activity of naringin and its aglycone by different in vitro assays. The effects of flavanones on lipid peroxidation, glutathione (GSH) oxidation and DNA cleavage were also assessed. RESULTS: The results showed that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin. Our results evidenced that glycosylation attenuated the efficiency in inhibiting the enzyme xanthine oxidase and the aglycone could act like a more active chelator of metallic ions than the glycoside. Additionally, naringenin showed a greater effectiveness in the protection against oxidative damage to lipids in a dose‐dependent manner. Both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH. CONCLUSION: The data obtained support the importance of characterizing the ratio naringin/naringenin in foods when they are evaluated for their health benefits. Copyright © 2010 Society of Chemical Industry     

The Falling Lake Victoria Water Level: GRACE,TRIMM and CHAMP Satellite Analysis of the Lake Basin

In the last 5 years, Lake Victoria water level has seen a dramatic fall that has caused alarm to water resource managers. Since the lake basin contributes about 20% of the lakes water in form of discharge, with 80% coming from direct rainfall, this study undertook a satellite analysis of the entire lake basin in an attempt to establish the cause of the decline. Gravity Recovery And Climate Experiment (GRACE), Tropical Rainfall Measuring Mission (TRMM) and CHAllenging Minisatellite Payload (CHAMP) satellites were employed in the analysis. Using 45 months of data spanning a period of 4 years (2002–2006), GRACE satellite data are used to analyse the variation of the geoid (equipotential surface approximating the mean sea level) triggered by variation in the stored waters within the lake basin. TRMM Level 3 monthly data for the same period of time are used to compute mean rainfall for a spatial coverage of .25°×.25° (25×25 km) and the rainfall trend over the same period analyzed. To assess the effect of evaporation, 59 CHAMP satellite’s occultation for the period 2001 to 2006 are analyzed for tropopause warming. GRACE results indicate an annual fall in the geoid by 1.574 mm/year during the study period 2002–2006. This fall clearly demonstrates the basin losing water over these period. TRMM results on the other hand indicate the rainfall over the basin (and directly over the lake) to have been stable during this period. The CHAMP satellite results indicate the tropopause temperature to have fallen in 2002 by about 3.9 K and increased by 2.2 K in 2003 and remained above the 189.5 K value of 2002. The tropopause heights have shown a steady increase from a height of 16.72 m in 2001 and has remained above this value reaching a maximum of 17.59 km in 2005, an increase in height by 0.87 m. Though the basin discharge contributes only 20%, its decline has contributed to the fall in the lake waters. Since rainfall over the period remained stable, and temperatures did not increase drastically to cause massive evaporation, the remaining major contributor is the discharge from the expanded Owen Falls dam.     

Tuning the Properties of CZTS Films by Controlling the Process Parameters in Cost-Effective Non-vacuum Technique

Highly dispersive Cu₂ZnSnS₄ (CZTS) nanoparticles were successfully synthesized by a simple solvothermal route. A low cost, non-vacuum method was used to deposit CZTS nanoparticle ink on glass substrates by a doctor blade process followed by selenization in a tube furnace to form Cu₂ZnSn (S,Se)₄ (CZTSSe) layers. Different selenization conditions and particle concentrations were considered in order to improve the crystallinity and surface morphology; the annealing temperature was varied between 400°C and 550°C and the annealing time was varied between 5 min and 20 min in a selenium-nitrogen atmosphere. The influence of annealing conditions on structural, compositional, optical and electrical properties of CZTSSe thin films was studied. An improvement in the structural and surface morphology was observed with increasing of annealing temperature (up to 500°C). An enhancement in the crystallinity and surface morphology were observed for thin films annealed for 10–15 min. Absorption study revealed that the band gap energy of as-deposited CZTS thin film was approximately 1.43 eV, while for CZTSSe thin films it ranged from 1.15 eV to 1.34 eV at different annealing temperatures, and from 1.33 eV to 1.38 eV for different annealing times.     

Zr‐Doped Indium Oxide (IZRO) Transparent Electrodes for Perovskite‐Based Tandem Solar Cells

Parasitic absorption in transparent electrodes is one of the main roadblocks to enabling power conversion efficiencies (PCEs) for perovskite‐based tandem solar cells beyond 30%. To reduce such losses and maximize light coupling, the broadband transparency of such electrodes should be improved, especially at the front of the device. Here, the excellent properties of Zr‐doped indium oxide (IZRO) transparent electrodes for such applications, with improved near‐infrared (NIR) response, compared to conventional tin‐doped indium oxide (ITO) electrodes, are shown. Optimized IZRO films feature a very high electron mobility (up to ≈77 cm² V^?1 s^?1), enabling highly infrared transparent films with a very low sheet resistance (≈18 Ω □^?1 for annealed 100 nm films). For devices, this translates in a parasitic absorption of only ≈5% for IZRO within the solar spectrum (250–2500 nm range), to be compared with ≈10% for commercial ITO. Fundamentally, it is found that the high conductivity of annealed IZRO films is directly linked to promoted crystallinity of the indium oxide (In₂O₃) films due to Zr‐doping. Overall, on a four‐terminal perovskite/silicon tandem device level, an absolute 3.5 mA cm^?2 short‐circuit current improvement in silicon bottom cells is obtained by replacing commercial ITO electrodes with IZRO, resulting in improving the PCE from 23.3% to 26.2%.