Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring

Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.     

Impact of the solidification path of FeOx–SiO2 slags on the resultant inorganic polymers

Aiming to reduce the carbon dioxide emissions associated with cement production, alternative binders such as inorganic polymers currently receive substantial attention and slags from the non-ferrous metallurgy are promising precursors. However, studies  that correlate their chemistry and crystallinity with the newly formed binder remain limited. In this work, the effect of three different solidification methods on glass formation and reactivity of FeO_x–SiO₂ slags, as well as on the molecular structure of the resultant Fe-rich inorganic polymers, was investigated. The inorganic polymers were synthesized by mixing the slags (approximate molar ratio FeO/SiO₂ = 1.6) with an alkali silicate solution (molar ratios SiO₂/Na₂O = 1.6 and H₂O/Na₂O = 25). Results demonstrated that higher cooling rates promoted higher glass formation and faster reaction kinetics when the slags were activated. ⁵⁷Fe Mössbauer spectroscopy indicated that all the slags consisted predominantly of Fe²⁺ ions with a minor amount of Fe³⁺ ions, regardless of the variability in glass content. The binder phase of all inorganic polymers consisted of iron in both Fe²⁺ and Fe³⁺ states, after 28 days of curing. After pulverizing the inorganic polymer pastes and exposing the powder to air for 28 additional days, the Fe²⁺ state in the binder transformed to Fe³⁺. The compressive strength evolution of the three slags showed that the 2-day strength was higher for the samples with a higher amorphous fraction, while after 28 days, this influence was less pronounced.     

Chitosan-based fiber-sponge materials as a promising tool for microalgae harvesting from Lake Baikal

Mass eutrophication of microalgae and cyanobacteria is observed in Lake Baikal in the past decade. In this paper, the concept of replaceable adsorption filter material based on chitosan flocculant filler and chlorinated polyvinyl chloride polymer nonwoven material are proposed. Functional and mechanical properties and morphology of the material are investigated depending on a packing density and a degree of chitosan filling. The introduction of 45% chitosan increases the Young's modulus up to 10 times, and it makes the material more rigid in 2.8 times. The high efficiency of sorption and growth inhibition of cumulative biomass culture was shown. The biomass source is taken from the coast of Barguzinsky Bay of Lake Baikal. Dominant species is microalgae of Scenedesmus genus.     

The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism

Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.     

Structural Consequences of the 1,2,3-Triazole as an Amide Bioisostere in Analogues of the Cystic Fibrosis Drugs VX-809 and VX-770

Although the 1,2,3-triazole is a commonly used amide bioisostere in medicinal chemistry, the structural implications of this replacement have not been fully studied. Employing X-ray crystallography and computational studies, we report the spatial and electronic consequences of replacing an amide with the triazole in analogues of cystic fibrosis drugs in the VX-770 and VX-809 series. Crystallographic analyses quantify subtle differences in the relative positions and conformational preferences of the R¹ and R² substituents attached to the amide and triazole bioisosteres. Computational studies derived from the X-ray data highlight the improved hydrogen bonding donor and acceptor capabilities of the amide in comparison to the triazole. This analysis of the spatial and electronic differences between the amide and 1,2,3-triazole will inform medicinal chemists as they consider using the triazole as an amide bioisostere.     

A comparative study of the purification of betanin

Betanin is a natural pigment with antioxidant properties used as a food colourant. This work describes the spectrophotometric and chromatographic quantification of betanin (2S/15S) and its epimer isobetanin (2S/15R) in fresh beetroot juice, food-grade beetroot powder and betanin standard diluted in dextrin. Absorption spectra of all three samples were deconvoluted using a mixed three-function model. Food-grade beetroot powder has the largest amount of violet-red impurities, probably formed during processing. The purification of betanin from these complex matrices was carried out by seven different methods. Ion exchange chromatography was the most efficient method for the purification of betanin from all samples; however, fractions contain high amounts of salt. Reversed-phase HPLC as well as reversed-phase column chromatography also produced good results at a much faster rate. The longer retention time of isobetanin when compared to betanin in reversed-phase conditions has been investigated by means of quantum-mechanical methods.     

Bacterial secretion of the Fab fragment of a mouse monoclonal IgM that reacts with IgG variable regions

In this report, we describe the expression system that enabledus to produce in Escherichia coli the Fab fragment of a mouseIgM that has previously been shown to inhibit the binding ofIgG to autoantigens by interacting with their variable regions.In our system, both light chain and heavy chain fragments wereput under the control of the malE promoter. The light chainwas fused to the MalE signal sequence, while the heavy chainvariable and first constant region were fused to the alkalinephosphatase signal sequence. In this system, after inductionof the promoter with maltose, the Fab fragment could be detectedin a periplasmic extract of the bacteria by Western blottingand also by ELISA. This Fab fragment was purified on a goatanti-mouse immunoglobulin immunoadsorbent and biotinylated.The Fab fragment produced by E.coli reacted with the trinitrophenyl(TNP) hapten and F(ab')₂ fragments of mouse IgG and these reactivitiescould be specifically inhibited by the corresponding solubleantigens. The dissociation constants of this Fab were 1.65 x10^–6 M for TNP and 5 x 10^–6 M for IgG F(ab')₂ fragments,indicating that the affinity of the Fab fragment compared withthat of the whole IgM molecule was similar for TNP but was lowerfor IgG F(ab')₂ fragments     

Microbial partitioning to settleable particles in stormwater

The degree to which microbes in the water column associate with settleable particles has important implications for microbial transport in receiving waters, as well as for microbial removal via sedimentation (i.e. detention basins). The partitioning behavior of several bacterial, protozoan and viral indicator organisms is explored in three urban streams under both storm and dry weather conditions. The fraction of organisms associated with settleable particles in stormwater is estimated through use of a centrifugation technique which is calibrated using suspensions of standard particles (e.g., glass, latex). The fraction of organisms associated with settleable particles varies by type of microbe, and the partitioning behavior of each organism generally changes between dry weather and storm conditions. Bacterial indicator organisms (fecal coliforms, Escherichia coli, enterococci) exhibited relatively consistent behavior, with an average of 20-35% of organisms associated with these particles in background samples and 30-55% in storm samples. Clostridium perfringens spores exhibited the highest average level of particle association, with storm values varying from 50% to 70%. Results related to total coliphage partitioning were more variable, with 20-60% associated with particles during storms. These estimates should be valuable in surface water quality modeling efforts, many of which currently assume that all microbes exist as free (unattached) organisms.     

Enhancement of etch rate for preparation of nano-sized ion-track membranes of poly(vinylidene fluoride): Effect of pretreatment and high-LET beam irradiation

We investigated how pretreatment and high-LET beam irradiation affected the ion-track dissolution rate in poly(vinylidene fluoride) (PVDF) films by SEM observations and conductometric analysis in order to develop the preparation methodology of nano-sized ion-track membranes. PVDF thin films irradiated with four types of ion beams were exposed to a 9 mol/dm³ KOH aqueous solution after their storage in air at 120 °C. This heating treatment was found to enhance the etch rate in the latent track, both in the inner core and outer halo regions, without changing that in the bulk, probably due to the formation of parasitic oxidation products facilitating the introduction of the etching agent to improve the etchability. Additionally, the irradiation of heavier higher-LET ions, causing each track to more activated sites (like radicals), was preferable for achieving effective etching.