Conditions Of Depletion Research Articles

Study of interface-trap and near-interface-state distribution in a 4H-SiC MOS capacitor with the full-distributed circuit model

In this research, the full-distributed circuit model was used to classify the contribution of interface traps (ITs) and near-interface states to the electrical characteristics of a 4H-SiC MOS capacitor over a wide range of operation. By fitting the measured capacitance and conductance at a certain value of applied gate voltage when the frequency varied from 1 kHz to 1 MHz, the density of both near-interface states and ITs was determined. The results reveal that, at RT, the frequency dispersion of capacitance in the depletion condition is mainly caused by the contribution of ITs. Nevertheless, in the strong accumulation condition, near-interface states become dominant for the frequency dispersion of the capacitance. Furthermore, the full-distributed circuit model also successfully explained the electrical characteristics of a 4H-SiC MOS capacitor when operating at 500 °C.

ENERGY EFFICIENCY PROCESS OF ANAEROBIC FERMENTATION OF ORGANICS WASTE

Anaerobic fermentation in biogas plants is an effective and promising method of manure disposal. During fermentation, especially in the thermophilic mode, animal excrement is largely disinfected, pathogenic microflora dies, weed seeds lose their germination and, in addition, biogas is released, the utilization of which allows to obtain additional energy. This way of utilization of manure under the conditions of gradual depletion and increase in the price of traditional sources acquires special importance. Since fermentation is carried out in closed facilities, completely isolated from the surrounding environment, the possibility of the spread of infections and gases with an unpleasant smell and the ingress of untreated manure into the soil, ground and underground water is eliminated. As a result of the decomposition of organic substances in the fermented product, the share of biogenic elements increases, most of them turn into mineral substances easily absorbed by plants, and nitrogen losses do not exceed 3-5%. An experimental installation was developed to determine the nature of gas release, the depth of mineralization of organic matter depending on the regime and design parameters, as well as with the purpose of developing, based on the obtained dependencies, technological schemes for anaerobic treatment and waste disposal of animal husbandry enterprises. The theoretical basis of mathematical modeling and forecasting of the operation of bioenergy plants is the material balance equation related to the rates of biochemical reactions and flow rates. The derivation of the material balance equation is possible if there is information about the hydraulic characteristics of bioenergy reactors, which depend on the operating conditions, limitations, and final results of the process. In addition, data on the rate of flow of biochemical reactions, the influence of environmental conditions and operating parameters on them are also necessary.

NCOA4 requires a [3Fe-4S] to sense and maintain the iron homeostasis

NCOA4 is a selective cargo receptor for ferritinophagy, the autophagic turnover of ferritin (FTH), a process critical for regulating intracellular iron bioavailability. However, how ferritinophagy flux is controlled through NCOA4 in iron-dependent processes needs to be better understood. Here, we show that the C-terminal FTH-binding domain of NCOA4 harbors a [3Fe-4S] binding site with a stoichiometry of approximately one labile [3Fe-4S] cluster per NCOA4 monomer. By analyzing the interaction between NCOA4 and HERC2 ubiquitin ligase or NCOA4 and FTH, we demonstrate that NCOA4 regulates ferritinophagy by sensing the intracellular iron-sulfur-cluster levels. Under iron repletion conditions, HERC2 recognizes and recruits holo-NCOA4 as a substrate for polyubiquitination and degradation, favoring ferritin iron storage. Under iron depletion conditions, NCOA4 exists in the form of apo-protein and binds ferritin to promote the occurrence of ferritinophagy and release iron. Thus, we identify an iron-sulfur cluster [3Fe-4S] as a critical cofactor in determining the fate of NCOA4 in favoring iron storage in ferritin or iron release via ferritinophagy and provide a dual mechanism for selective interaction between HERC2 and [3Fe-4S]-NCOA4 for proteasomal degradation or between ferritin and apo-NCOA4 for ferritinophagy in the control of iron homeostasis.

Problems complicating the introduction of technogenic deposits into economic circulation

Relevance. In modern conditions of depletion of the mineral resource base, deterioration of natural conditions of newly discovered deposits, the development of technogenic mineral resources gains primary importance. However, as the analysis shows, the level of use of solid mineral formations continues to remain insignificant. The purpose of the study is to identify the reasons that slow down the process of involving technogenic deposits into economic circulation, in order to prevent their occurrence or mitigate negative impacts. Research methods. In the research process, methods of comparative analysis, analogies, and expert analysis were used. Results. Analysis and generalization of domestic and foreign experience in the management of technogenic mineral formations (TMFs) allowed us to identify the main reasons hindering the expansion of the practice of developing technogenic deposits. Nine reasons were identified: imperfection of the regulatory framework for the management of TMFs, low degree of geological knowledge, high geological risk, lack of waste processing technologies, lack of necessary financial resources, imperfection of the economic mechanism used by the state in regulating waste management activities, the possibility of extending shelf life of TMFs, imperfect availability of information about TMFs, lack of qualified personnel. As a result of an expert survey of 20 specialists, the identified reasons were ranked and the highest priorities were identified. These included: the imperfection of the regulatory framework, the lack of environmentally friendly technologies required and the lack of an effective economic mechanism for state regulation of this activity. Conclusions. Identification of the primary reasons slowing down the process of development of technogenic deposits determines the further direction of work to prevent them or mitigate negative impacts.

Association of <i>NR3C1 Bcl1</i> gene polymorphism with impaired programmed cell death of lymphocytes in patients with atopic bronchial asthma

Atopic asthma is a chronic disease characterized by airway obstruction, bronchial hyperresponsiveness, and inflammation. Patients show increased activation of immune cells in the airways, especially T-lymphocytes, leading to chronic inflammation. The lymphocytes of asthma patients are known to have an impairment of the type 1 and 2 programmed cell death, i.e., apoptosis and autophagy, thus contributing to prolongation and intensification of inflammatory process. As compared to apoptosis, autophagy may also contribute to cell survival under stress conditions. Its disruption and hyperactivation leads to exacerbation of allergic responses. Glucocorticoids are the main drugs for the treatment of atopic bronchial asthma by activating the glucocorticoid receptor, thus triggering anti-inflammatory response and apoptosis of the cells. However, some patients exhibit resistance to therapy due to various factors, including single nucleotide polymorphisms of NR3C1 glucocorticoid receptor gene. The highest association between asthma severity and resistance to therapy was found for the GG variant of the NR3C1 Bcl1 polymorphism. Common molecular pathways for glucocorticoid receptor activation and programmed cell death and mediating molecules suggest a significant role for the polymorphic receptor variant in cell death. The aim of our study was to evaluate the effect of a single nucleotide polymorphism (G allele, i.e., Bcl1 polymorphism of NR3C1 gene) of glucocorticoid receptor on expression levels of genes that regulate apoptosis (BCL2, CASP3) and autophagy (BECN1, LC3) in lymphocytes of patients with moderate and severe atopic bronchial asthma. The study was performed with peripheral blood samples of 24 patients aged 20 to 45 years with an established diagnosis of moderate to severe atopic bronchial asthma. Using PCR technique with restriction fragment length polymorphism (RFLP) assay, the patients were distributed according to the genotypes of the BclI polymorphism of the NR3C1 gene: 12 patients with CC genotype, 8 persons with GC genotype, and 4 cases with GG genotype. The lymphocytes were isolated in Ficoll density gradient and cultivated with dexamethasone under the conditions of nutrient depletion. The level of gene expression was determined by real-time PCR. When studying associations between various genotypes of Bcl1 polymorphism and expression of cell death marker genes, the anti-apoptotic reactions were detected in lymphocytes of patients with GG polymorphism under the influence of dexamethasone thus being a potential mechanism for development of resistance to glucocorticosteroid therapy in asthma. Impaired activation of BECN1 gene expression in patients with the GG genotype may suggest deregulation of the autophagy in this group of patients, as a mode of programmed cell death. Moreover, in patients with GC genotype during long-term cultivation, exposure to dexamethasone increases the expression of the LC3 gene, indicating a more pronounced activation of autophagy. Hence, this work demonstrates differences in response of lymphocytes to synthetic glucocorticoid therapy, and probable effect of G allele (Bcl1 polymorphism) on dysregulation of programmed cell death under the influence of dexamethasone.

Rapid ozone depletion after humidification of the stratosphere by the Hunga Tonga Eruption.

The eruption of the Hunga Tonga-Hunga Ha'apai volcano on 15 January 2022 offered a good opportunity to explore the early impacts of tropical volcanic eruptions on stratospheric composition. Balloon-borne observations near Réunion Island revealed the unprecedented amount of water vapor injected by the volcano. The enhanced stratospheric humidity, radiative cooling, and expanded aerosol surface area in the volcanic plume created the ideal conditions for swift ozone depletion of 5% in the tropical stratosphere in just 1 week. The decrease in hydrogen chloride by 0.4 parts per million by volume (ppbv) and the increase in chlorine monoxide by 0.4 ppbv provided compelling evidence for chlorine activation within the volcanic plume. This study enhances our understanding of the effect of this unusual volcanic eruption on stratospheric chemistry and provides insights into possible chemistry changes that may occur in a changing climate.

Spatial-temporal Trends Mapping and Geostatistical Modelling of Groundwater Level Depth Over Northern Parts of Indo-Gangetic Basin, India

Haryana-Punjab is a vast part of the Indo-Gangetic basin (India), recognised globally as a major hotspot of groundwater abstraction and agricultural economic reliance. A lack of information is present in this region regarding spatiotemporal changes in groundwater levels. Geostatistical anisotropic processes are reliable, especially when the monitored regions are extensive. The modelling study involves a twofold objective. First, it estimates and evaluates anisotropic spatial variations in groundwater level depth (GWD, Surface to water level) using geostatistics for all four seasons of Indian cropping patterns—pre-monsoon, monsoon, post-monsoon (rabi) and post-monsoon (Kharif), and parameters of point kriging cross-validation (PKCV) are optimum, acceptable, and support the unbiasedness hypothesis of kriging. Based on the PKCV, five essential parameters were computed to accept the anisotropy semi-variogram fitted model. These are (1) kriging mean error (KME), ideally close to zero so that there are no over or underestimates, (2) goodness of fit (R2), (3) the ratio of estimated variance (EV) to kriging variance (KV) lies between 0.95-1.05, (4) good eye visualisation fit and (5) significant t-test on the correlation coefficient. The second objective is spatiotemporal modelling, a pixel-based Mann-Kendall trend testing (at 95% Confidence Interval) on kriged raster surfaces of GWD (For all four seasons) at 1km grid resolution. The trend, significant or not, is determined by the Mann-Kendall test, while Sen's slope estimator determines the slope magnitude of the trend. Results revealed that the study area's east-central to the central-northern region comes under a high depletion zone for groundwater levels. GWD significantly increased by 120cm/year-80cm/year in this region, and the mean kriged GWD for the entire study area increased by 30cm/year-29cm/year over 25 years. Seasonal climatological mean maps of kriged surfaces of GWD and mean rainfall surfaces in two different time phases for all four seasons have been evaluated. It is observed from these maps that wherever the rainfall is increasing, GWD is decreasing. Results clarified that anisotropic semi-variogram modelling with kriging, pixel-based trend analysis, and regression studies is a valuable tool for identifying the critical region of groundwater levels, and the central region of the study area falls under the severe depletion condition of the groundwater level.

Alkaline phosphatase LapA regulates quorum sensing-mediated virulence and biofilm formation in Pseudomonas aeruginosa PAO1 under phosphate depletion stress.

Among various environmental stresses, the depletion of inorganic phosphate, which is an important signaling molecule that modulates virulence production, is notable. In our previous study, we demonstrated that lapA, encoding alkaline phosphatase, plays a key role in Pseudomonas aeruginosa biofilm formation in porcine skin explants, an ex vivo chronic wound model. However, the mechanism by which lapA participates in the virulence and biofilm formation of P. aeruginosa remains unclear. In the present study, the lapA deletion mutant was constructed in P. aeruginosa PAO1, and the phenotypic characterization was assessed. Our data demonstrated that phosphate depletion stress significantly enhanced elastase activity, hemolysis, rhamnolipid production, swarming and swimming motilities, and 3-oxo-C12-homoserine lactone (HSL) production in P. aeruginosa. Moreover, phosphate starvation evidently induced the virulence of P. aeruginosa in Caenorhabditis elegans (C. elegans) through fast-kill and slow-kill infections. Deletion of the lapA gene led to broad phenotypic changes, including reduced elastase activity, swimming motility, C4-HSL, and 3-oxo-C12-HSL production, as well as increased chitinase activity and rhamnolipid production under phosphate depletion stress, which was unrelated to C4-HSL. Deletion of the lapA gene also significantly inhibited PAO1 biofilm formation in porcine skin explants by reducing the expression levels of las and rhl quorum sensing systems and extracellular polymeric substance synthesis. Finally, lapA deletion also reduced the virulence of PAO1 in C. elegans in fast-kill and slow-kill infection assays. Thus, the findings suggest that targeting lapA can help control biofilm formation and reduce virulence in nonhealing-infected wounds, where P. aeruginosa is a persistent problem. IMPORTANCE Our previous study demonstrated that the expression of lapA was induced under phosphate depletion conditions, but its roles in virulence and biofilm formation by Pseudomonas aeruginosa remain largely unknown. This study presents a systematic investigation of the roles of lapA in virulence induction and biofilm formation by constructing a lapA-deficient strain with P. aeruginosa PAO1. The results showed that deletion of the lapA gene evidently reduced elastase activity, swimming motility, C4-HSL, and 3-oxo-C12-HSL production, and increased rhamnolipid production under phosphate depletion stress. Moreover, lapA gene deletion inhibited PAO1 biofilm formation in porcine skin explants by reducing the expression levels of las and rhl quorum sensing systems and extracellular polymeric substance synthesis. Finally, lapA gene deletion also reduced the virulence of PAO1 in Caenorhabditis elegans in fast-kill and slow-kill infection assays. This study provides insights into the roles of lapA in modulating P. aeruginosa virulence and biofilm formation under phosphate depletion stress.

How managers can help employees navigate tough decisions without burning out

This paper examines the dilemma of having to perform a resource-intensive task under conditions of resource depletion. Drawing from data on resource-depleting tasks in multiple contexts, we document three distinct forms of self-management (equipping, conserving, and restoring the self) that individuals use across three distinct phases of the task (preparation, execution, transition) to manage psychological resources, and we detail the particular practices used to serve each of these core resource management functions. We offer a series of practical suggestions for organizations to help employees manage these psychologically difficult tasks.

Bimetallic Ru1−xVxO2 and trimetallic Ru1−x−yVxCryO2 alloy nanofibers for efficient, stable and pH-independent oxygen evolution reaction catalysis

We present ruthenium-vanadium mixed alloy metal oxide (Ru1−xVxO2) nanofibers as well as chromium (Cr) doped Ru1−x−yVxCryO2 nanofibers using electrospinning and subsequent thermal annealing procedures as cost-effective, highly active and stable electrocatalyst for oxygen evolution reaction (OER). Both Ru1−xVxO2 and Ru1−x−yVxCryO2 nanofibers exhibited tetragonal crystalline structure, confirming that Ru, V, and Cr ions randomly occupied the tetragonal lattice sites due to the similar ionic sizes. Both Ru1−xVxO2 and Ru1−x−yVxCryO2 nanofibers showed excellent OER electrocatalytic activity, characterized by low overpotentials and small Tafel slopes, in both acidic and alkaline conditions. Ru1−xVxO2 (x = 0.52) nanofibers demonstrated an enhanced elemental substitution effect, leading to an enlarged active surface area that contributed to their exceptional OER activity. Ru1−x−yVxCryO2 nanofibers, achieved through optimal doping with Cr4+ ions, not only displayed significantly improved stability but also exhibited high OER activity. Interestingly, both Ru1−xVxO2 and Ru1−x−yVxCryO2 nanofibers consistently catalyzed alkaline OER, even under conditions of reactant depletion. These nanofibers, containing noble Ru with less than half of the total metal content, are proposed as efficient and cost-effective OER catalysts for use in both acidic and alkaline media.

Zinc depletion induces JNK/p38 phosphorylation and suppresses Akt/mTOR expression in acute promyelocytic NB4 cells

BackgroundMyeloid leukemia is associated with reduced serum zinc and increased intracellular zinc. Our previous studies found that zinc depletion by TPEN induced apoptosis with PML-RARα oncoprotein degradation in acute promyelocytic NB4 cells. The effect of zinc homeostasis on intracellular signaling pathways in myeloid leukemia cells remains unclear. ObjectiveThis study examined how zinc homeostasis affected MAPK and Akt/mTOR pathways in NB4 cells. MethodsWe used western blotting to detect the activation of p38 MAPK, JNK, ERK1/2, and Akt/mTOR pathways in NB4 cells stimulated with the zinc chelator TPEN. Whether the effects of TPEN on these pathways could be reversed by zinc or the nitric oxide donor sodium nitroprusside (SNP) was further explored by western blotting. We used Zinpyr-1 staining to assess the role of SNP on labile zinc levels in NB4 cells treated with TPEN. In additional, we evaluated expressional correlations between the zinc-binding protein Metallothionein-2A (MT2A) and genes related to MAPKs and Akt/mTOR pathways in acute myeloid leukemia (AML) based on the TCGA database. ResultsZinc depletion by TPEN activated p38 and JNK phosphorylation in NB4 cells, whereas ERK1/2 phosphorylation was increased first and then decreased. The protein expression levels of Akt and mTOR were downregulated by TPEN. The nitric oxide donor SNP promotes zinc release in NB4 cells under zinc depletion conditions. We further found that the effects of zinc depletion on MAPK and Akt/mTOR pathways in NB4 cells can be reversed by exogenous zinc supplementation or treatment with the nitric oxide donor SNP. By bioinformatics analyses based on the TCGA database, we demonstrated that MT2A expression was negatively correlated with the expression of JNK, and was positively correlated with the expression of ERK1 and Akt in AML. ConclusionOur findings indicate that zinc plays a critical role in leukemia cells and help understanding how zinc depletion induces apoptosis.

“Ca2+-dependent regulation of the proton permeability of the inner membrane of lupine cotyledon mitochondria”

change in volume, and proton permeability of the inner membrane of mitochondria isolated from cotyledons of etiolated seedlings of narrow-leaved lupine (Lupinus angustifolius L.) was studied. The mitochondria used in the work were characterized by a strong coupling of oxidation and phosphorylation processes. The high functional activity of mitochondria was confirmed by their ability to generate a transmembrane gradient of protons on the inner membrane (membrane potential or ∆Ψ) during the oxidation of succinate and also sustainably maintain it for a long time , both due to the operation of the electron transport chain and due to ATP hydrolysis under conditions of anaerobiosis. It was shown that the presence of 60–120 µM CaCl2 in the mitochondrial incubation medium had no significant effect on the rate of succinate oxidation and the parameters of oxidative phosphorylation; however, it induced ∆Ψ dissipation under conditions of oxygen depletion in the incubation medium. The most complete removal Ca2+ from the medium in the presence of chelators (EGTA, EDTA) prevented the membrane potential dissipation. Ca2+-dependent depolarization of the inner membrane was inhibited by dithiothreitol, suggesting involvement in this process of reactive oxygen species. The reset of the membrane potential was not accompanied by swelling of mitochondria and was not sensitive to cyclosporine A. Using metallochromic Ca2+-indicator arsenazo III, it was shown that the mitochondria of lupine cotyledons are able to actively absorb exogenous Ca2+ and store it in the matrix. Ca2+-induced dissipation of ∆Ψ under conditions of anaerobiosis was accompanied by the release of Ca2+ from mitochondria, the rate of which sharply increased in the presence of calcium ionophore A23 (A23187). It is assumed that the accumulation of Ca2+ and an increase in the level of reactive oxygen species in the matrix induces reversible permeabilization of the inner mitochondrial membrane of lupine cotyledons under conditions of anaerobiosis, which is due to the opening of a pore of nonspecific permeability in a state of low conductivity permeable to protons and, possibly, to other small cations (Na+, K+, Ca2+).

Modelling ligand depletion for simultaneous affinity and binding site quantification on cells and tissue

The quantification of the number of targets in biological systems is an important parameter to assess the suitability of surface markers as targets for drugs, drug delivery and medical imaging. Likewise, quantifying the interaction with the target in terms of affinity and binding kinetics is essential during drug development. Commonly used approaches to quantify membrane antigens on live cells are based on manual saturation techniques that are labour-intensive, require careful calibration of the generated signal and do not quantify the binding rates. Here, we present how measuring interactions in real-time on live cells and tissue under ligand depletion conditions can be used to simultaneously quantify the kinetic binding parameters as well as the number of available binding sites in a biological system. Suitable assay design was explored with simulated data and feasibility of the method verified with experimental data for exemplary low molecular weight peptide and antibody radiotracers as well as fluorescent antibodies. In addition to revealing the number of accessible target sites and improving the accuracy of binding kinetics and affinities, the presented method does not require knowledge about the absolute signal generated per ligand molecule. This enables a simplified workflow for use with both radioligands and fluorescent binders.

Сell model for experimental research in keratoconus pathogenesis

INTRODUCTION: Certain mineral elements dismetabolism is known to play an important part in the pathogenesis of the corneal degenerative and dystrophic diseases, as metalloenzymes participate in connective tissues metabolism affecting their properties. Thus, in keratoconus corneal tissue is depleted in iron, copper and zinc, what could be the underlying cause of cornea biomechanical properties impairment. Keratoconus modeling is complicated and practically not reproducible in animals, therefore cell models elaboration is very much in demand. Definite mineral elements content must be reduced in order to simulate pathological changes specific for keratoconic corneas.
 PURPOSE: The aim of this study was an elaboration of a cell model suitable for keratoconus pathogenesis research. This goal achieving involved solving the following tasks: 1) to develop a tissue-engineered system that mimic healthy corneal stroma; 2) to develop a technique for selective depletion of the nutrient medium by mineral elements involved in keratoconus pathogenesis; 3) to assess the possibility of the designed tissue-engineered system growth in the depleted nutrient medium.
 MATERIAL AND METHODS: The study was carried out with the primary culture of human keratocytes, which were used to build tissue-engineered systems of three types: on silicone, on a membrane, without a carrier. Cell cultures morphology was evaluated by light and electron microscopy. The nutrient media were zinc depleted via decationization of fetal bovine serum using two types of ion-exchange resins; mineral elements concentrations were evaluated by means of inductively coupled plasma mass spectrometry.
 RESULTS: The tissue system engineered without a carrier in form of cell sheet was chosen as the most convenient model. The decationization of the serum by means of Chelex 100 resin was shown to be a successful method for tenfold zinc concentration reduction in the nutrient medium. Keratocytes cultivation in the form of cell sheet on a zinc-depleted medium was successfully approved.
 CONCLUSION: Elaborated tissue-engineered system could be considered as a model of the corneal stroma under specific for keratoconus conditions of zinc depletion.

STANDART DISPLACEMENT CHARACTERISTICS AS AN EXPRESS METHOD FOR ANALYSIS AND MONITORING OF OIL FIELD DEVELOPMENT

The main task currently facing oil companies is to increase the efficiency of oil production in conditions of depletion of traditional reserves. The deposits of the West Siberian oil and gas basin are mainly at the third and fourth stages of development (final), which are characterized by a deterioration in oil flow rates, an increase in the water content of the extracted products, as well as the involvement of hard-to-recover reserves in the development. Field development specialists need to respond promptly to the events that led to a decrease in oil production in a short time in the absence of creating a complete geological and hydrodynamic model. Consequently, there is a need to develop a methodology that will allow you to quickly identify and localize problem areas of the development object in order to optimize costs, and most importantly, increase or maintain target production for maximum reserves production. In this regard, it is proposed to use the synergy of the developed approaches - the division of development objects into blocks and the construction of reference characteristics of displacement. The blocks, in turn, allow you to analyze the development of the object most reliably, and carry out calculations much faster. The reference characteristics of displacement show themselves as a tool that allows you to evaluate the effectiveness of flooding during the development of an object with a formed reservoir pressure maintenance system, also demonstrates the production of reserves, the effectiveness of flooding and production. In this study, an algorithm for analyzing the development of the block is considered in detail, both from the energy state and the development of reserves, according to which geological and technical measures for the intensification of production are determined.

Multi-Electron Transfer at H-Terminated p-Si Electrolyte Interfaces: Large Photovoltages under Inversion Conditions.

Photovoltages for hydrogen-terminated p-Si(111) in an acetonitrile electrolyte were quantified with methyl viologen [1,1'-(CH3)2-4,4'-bipyridinium](PF6)2, abbreviated MV2+, and [Ru(bpy)3](PF6)2, where bpy is 2,2'-bipyridine, that respectively undergo two and three one-electron transfer reductions. The reduction potentials, E°, of the two MV2+ reductions occurred at energies within the forbidden bandgap, while the three [Ru(bpy)3]2+ reductions occurred within the continuum of conduction band states. Bandgap illumination resulted in reduction that was more positive than that measured with a degenerately doped n+-Si demonstrative of a photovoltage, Vph, that increased in the order MV2+/+ (260 mV) < MV+/0 (400 mV) < Ru2+/+ (530 mV) ∼ Ru+/0 (540 mV) ∼ Ru0/- (550 mV). Pulsed 532 nm excitation generated electron-hole pairs whose dynamics were nearly constant under depletion conditions and increased markedly as the potential was raised or lowered. A long wavelength absorption feature assigned to conduction band electrons provided additional evidence for the presence of an inversion layer. Collectively, the data reveal that the most optimal photovoltage, as well as the longest electron-hole pair lifetime and the highest surface electron concentration, occurs when E° lies energetically within the unfilled conduction band states where an inversion layer is present. The bell-shaped dependence for electron-hole pair recombination with the surface potential was predicted by the time-honored SRH model, providing a clear indication that this interface provides access to all four bias conditions, i.e., accumulation, flat band, depletion, and inversion. The implications of these findings for photocatalysis applications and solar energy conversion are discussed.

Impact of the Stimulation and Inhibition of NAD&lt;sup&gt;+&lt;/sup&gt; Biosynthesis on the Maintenance of Pluripotency in Mouse Embryonic Stem Cells

Nicotinamide adenine dinucleotide (NAD+) plays a key role in cellular metabolism and signaling. In recent years, evidence has accumulated that NAD+-dependent processes are involved in the regulation of pluripotency and differentiation of mammalian embryonic stem cells. The major means to maintain NAD+ levels in mammalian cells is through its biosynthesis from various forms of vitamin B3. In this study, we examined how stimulation and inhibition of NAD+ biosynthesis affect the maintenance of the pluripotency of mouse embryonic stem cells E14 Tg2a (E14 cells). The pluripotency status of E14 cells was assessed by immunocytochemical and immunoblotting analysis using antibodies to the pluripotency factor Oct4, as well as by staining for alkaline phosphatase. Using NMR spectroscopy, we have found that the concentration of NAD+ in pluripotent E14 cells cultured in the presence of LIF is about 4 nmol/mg, and it remains unchanged after induction of differentiation with retinoic acid. We have also demonstrated that pharmacological stimulation of NAD+ biosynthesis by nicotinamide riboside increases the level of intracellular NAD+ by 20%, but it does not affect the maintenance of pluripotency in E14 cells. Moreover, under conditions of critical depletion of NAD+ pool by Nampt inhibition with FK866 E14 cells maintained pluripotency, though the expression level of Oct4 was decreased.

Cholesterol biosynthesis modulates differentiation in murine cranial neural crest cells

Cranial neural crest cells (cNCC) are a multipotent embryonic cell population that give rise to a diverse set of cell types. These cells are particularly vulnerable to external metabolic stressors, as exemplified by the association between maternal hyperglycemia and congenital malformations. We were interested in studying the effect of various concentrations of glucose and pyruvate on cNCC metabolism, migration, and differentiation using an established murine neural crest cell model (O9-1). We unexpectedly observed a pattern of gene expression suggestive of cholesterol biosynthesis induction under glucose depletion conditions in O9-1 cells. We further showed that treatment with two different cholesterol synthesis inhibitors interfered with cell migration and differentiation, inhibiting chondrogenesis while enhancing smooth muscle cell differentiation. As congenital arhinia (absent external nose), a malformation caused by mutations in SMCHD1, appears to represent, in part, a defect in cNCC, we were also interested in investigating the effects of glucose and cholesterol availability on Smchd1 expression in O9-1 cells. Smchd1 expression was induced under high glucose conditions whereas cholesterol synthesis inhibitors decreased Smchd1 expression during chondrogenesis. These data highlight a novel role for cholesterol biosynthesis in cNCC physiology and demonstrate that human phenotypic variability in SMCHD1 mutation carriers may be related, in part, to SMCHD1’s sensitivity to glucose or cholesterol dosage during development.

Vegetal-derived biostimulants distinctively command the physiological and metabolomic signatures of lettuce grown in depleted nitrogen conditions

Biostimulants are sustainable inputs that can be used to reduce chemical fertilizers dependency while reinforcing nutrient uptake, yield and quality of crops, and modulate plant metabolic processes. Protein hydrolysates (PHs) are prominent biostimulants that guarantee a reduction in yield loss under sub-optimal nitrogen (N) conditions. On these bases, a new Malvaceae-derived PH product was tested along a commercial legume-derived PH on soilless greenhouse-grown lettuce, to comparatively assess their activity under N depletion conditions (1 mM NO3−). Both PHs increased biometric parameters under optimal but to a lesser extent under depleted N conditions. Legume-derived PH promoted greater Fv/Fm, lutein and β-carotene under optimal N conditions and higher catalase and total phenolic acids. In contrast, Malvaceae-derived PH did not affect phenolic acids but increased leaf concentration of Ca, Mg and catalase while reducing H2O2. Biochemical changes were then evaluated through untargeted metabolomics. Metabolomics showed a hierarchically prevalent effect of the N level, with the PHs showing distinctive reprogramming under optimal and depleted N conditions. Among others, phenylpropanoids were mainly down-accumulated in stressed plants, while (polyunsaturated fatty acids) PUFA accumulated following the application of PHs. Notwithstanding, the severe depletion of N cannot be compensated by PHs treatment since biostimulants are used to complement fertilizers use and not to replace it.

PARP1 Regulates Circular RNA Biogenesis though Control of Transcriptional Dynamics.

Circular RNAs (circRNAs) are a recently discovered class of RNAs derived from protein-coding genes that have important biological and pathological roles. They are formed through backsplicing during co-transcriptional alternative splicing; however, the unified mechanism that accounts for backsplicing decisions remains unclear. Factors that regulate the transcriptional timing and spatial organization of pre-mRNA, including RNAPII kinetics, the availability of splicing factors, and features of gene architecture, have been shown to influence backsplicing decisions. Poly (ADP-ribose) polymerase I (PARP1) regulates alternative splicing through both its presence on chromatin as well as its PARylation activity. However, no studies have investigated PARP1's possible role in regulating circRNA biogenesis. Here, we hypothesized that PARP1's role in splicing extends to circRNA biogenesis. Our results identify many unique circRNAs in PARP1 depletion and PARylation-inhibited conditions compared to the wild type. We found that while all genes producing circRNAs share gene architecture features common to circRNA host genes, genes producing circRNAs in PARP1 knockdown conditions had longer upstream introns than downstream introns, whereas flanking introns in wild type host genes were symmetrical. Interestingly, we found that the behavior of PARP1 in regulating RNAPII pausing is distinct between these two classes of host genes. We conclude that the PARP1 pausing of RNAPII works within the context of gene architecture to regulate transcriptional kinetics, and therefore circRNA biogenesis. Furthermore, this regulation of PARP1 within host genes acts to fine tune their transcriptional output with implications in gene function.