Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response,Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.     

Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD

Alterations in mitochondrial function are an important control variable in the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), while also noted by increased de novo lipogenesis (DNL) and hepatic insulin resistance. We hypothesized that the organization and function of a mitochondrial electron transport chain (ETC) in this pathologic condition is a consequence of shifted substrate availability. We addressed this question using a transgenic mouse model with increased hepatic insulin resistance and DNL due to constitutively active human SREBP-1c. The abundance of ETC complex subunits and components of key metabolic pathways are regulated in the liver of these animals. Further omics approaches combined with functional assays in isolated liver mitochondria and primary hepatocytes revealed that the SREBP-1c-forced fatty liver induced a substrate limitation for oxidative phosphorylation, inducing enhanced complex II activity. The observed increased expression of mitochondrial genes may have indicated a counteraction. In conclusion, a shift of available substrates directed toward activated DNL results in increased electron flows, mainly through complex II, to compensate for the increased energy demand of the cell. The reorganization of key compounds in energy metabolism observed in the SREBP-1c animal model might explain the initial increase in mitochondrial function observed in the early stages of human MAFLD.     

Neurochemical Alterations in Social Anxiety Disorder (SAD): A Systematic Review of Proton Magnetic Resonance Spectroscopic Studies

(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (¹H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using ¹H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the ‘fear neurocircuitry’ in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.     

UNICORE 6 — Recent and Future Advancements

UNICORE is a European Grid Technology with more than 10 years of history. Originating from the Supercomputing domain, the latest version UNICORE 6 has turned into a general-purpose Grid technology that follows established standards and offers a rich set of features to its users. The paper starts with an architectural insight into UNICORE 6, highlighting the workflow features, standards and the different clients. Next, the current state of advancement is presented by describing recent developments. The paper closes with an outlook on future planned developments.     

Core‐Brominated Tetraazaperopyrenes as n‐Channel Semiconductors for Organic Complementary Circuits on Flexible Substrates

Organic thin‐film transistors (TFTs) are prepared by vacuum deposition and solution shearing of 2,9‐bis(perfluoroalkyl)‐substituted tetraazaperopyrenes (TAPPs) with bromine substituents at the aromatic core. The TAPP derivatives are synthesized by reacting known unsubstituted TAPPs with bromine in fuming sulphuric acid, and their electrochemical properties are studied in detail by cyclic voltammetry and modelled with density functional theory (DFT) methods. Lowest unoccupied molecular orbital (LUMO) energies and electron affinities indicate that the core‐brominated TAPPs should exhibit n‐channel semiconducting properties. Current‐voltage characteristics of the TFTs established electron mobilities of up to μ_n = 0.032 cm² V^?1 s^?1 for a derivative which was subsequently processed in the fabrication of a complementary ring oscillator on a flexible plastic substrate (PEN).     

Determination of Glyphosate and Its Metabolite AMPA (Aminomethylphosphonic Acid) in Cereals After Derivatization by Isotope Dilution and UPLC-MS/MS”

A straightforward analytical method has been developed for the determination of glyphosate and aminomethylphosphonic acid (AMPA), its major metabolite in cereals. This method entails a rapid extraction and derivatization with 9-fluorenylmethyl chloroformate followed by separation with a conventional reversed-phase rapid chromatography used in daily routine analysis and detection by electrospray ionization tandem mass spectrometry. To overcome matrix effects and compensate for any analyte losses during sample treatment, an isotopic dilution approach was used. Since 2010, the monitoring of cereals for the widely used herbicide glyphosate is obligatory to all European Union (EU)-member states, laid down in Commission Regulation (EC) No. 1213/2008. Hence, there is definitively a need for a reliable and easy-to-handle analytical method for monitoring of this compound. The proposed method can be run without having to make time-consuming changes on the equipment used for daily routine analysis. The analytical performance of the method was evaluated according to SANCO/10684/2009 criteria and demonstrated that this method is rugged and cost-effective, therefore suitable for monitoring purposes as well as legislative enforcements within the EU. The apparent recoveries of both analytes were between 97% and 113% with relative standard deviations less than 20%. The limits of quantification of glyphosate and AMPA were 0.02 mg/kg in cereal matrices. Finally, the accuracy of the method was assessed by analyzing a proficiency test material which was available from a previous round (EUPT-C4).     

Diamine oxidase supplementation improves symptoms in patients with histamine intolerance

Food Science and Biotechnology - Histamine intolerance (HIT) is thought to be caused by a disproportionate amount of histamine in the body. The enzyme diamine oxidase (DAO) is considered for the...     

Effect of maturation conditions on sensory and antioxidant properties of old Serbian plum brandies

?ljivovica and Prepe?enica are traditional Serbian distillated beverages made from varieties of plum, of the genus Prunus. The ageing in wooden casks not only improves the sensory characteristics, but also changes the content of total polyphenols and contributes to the other important health properties, such as the increase of their antioxidant capacity. In this study, home-made brandy (?ljivovica and Prepe?enica) samples were used, which matured in casks during the time period from 10 to 47?years. The aim of this investigation was to examine the influence of the ageing parameters (time period and type of wooden casks) and raw material (plum cultivars) on the total polyphenol content, amount of certain phenol compounds, sensory properties, colour and antioxidant properties in matured brandies. The individual phenol components were determinated using HPLC system equipped with diode array detector, while the total phenol content and antioxidant activity was estimated using spectrophotometric methods (Folin?CCiocalteu, DPPH, FRAP and TEAC). Total polyphenol content (TPC) of aged Prepe?enica samples was ranged from 230.26 to 890.26?mg/L gallic acid equivalents (GAE mg/L), whereas the TPC of ?ljivovica sample was 110.38?mg/L. Antioxidant capacity of analysed Prepe?enica samples and ?ljivovica sample was in strong correlation with TPC. Total sensory score of all samples was very high and varied between 18.2 and 19.8. The obtained results have shown that the benefit of longer maturation on sensory characteristics is well recognized, but the improvement has some limitation.     

Yeasts isolated from three varieties of grapes cultivated in different locations of the Dolenjska vine-growing region, Slovenia

The number and diversity of yeasts on grape berry surfaces are influenced by several factors, such as grape variety, degree of grape maturity at harvest, climatological conditions, geographic location, physical damage of grapes, the intensity of pest management etc. Cvicek is a typical Slovene wine, which has obtained a special protection under the Slovene Wine Law for its geographical origin. This blended red wine is produced from different grape varieties (Vitis vinifera L.), mostly from red grapes of Zametovka and Modra frankinja and from white grapes of Kraljevina. The aim of this study was to evaluate the impact of geographical locations in the Dolenjska vine-growing region and to obtain precise information about the influence of different grape varieties on the composition of yeast community on grape berries. The restriction fragment length polymorphism of PCR-amplified fragments from the rDNA gene cluster (PCR RFLP of rDNA) has been used for the differentiation of yeast species. The standard identification procedure has been performed on representative strains that shared identical RFLP profiles. The number of yeasts and yeast species isolated varied according to different grape varieties, Zametovka, Modra frankinja and Kraljevina (V. vinifera L.) and according to different sampling location. On the surface of grape berries 13 different yeast species have been identified. Saccharomyces cerevisiae has not been found.     

Antioxidant and cell growth activities of beet root pomace extracts

Beetroot (Beta vulgaris) pomace, processing by-product from food industry, was investigated in this work as a starting raw material. The contents of phenolics (1.87–11.98 mg GAE/g of dry weight) and betalains (0.75–3.75 mg betalains/g of dry weight) in the extracts were determinated spectrophotometrically. Some individual phenolic compounds, including ferulic, vanillic, p-hydroxybenzoic, caffeic and protocatehuic acids, were identified and quantified by HPLC. The antioxidative activity of beetroot extracts was tested using DPPH, hydroxyl and superoxide anion radicals by ESR spectroscopy. ${\text{IC}}_{50}^{{}^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}}\text{OH}}$ (0.05–0.108 mg/ml), $\text{IC}{50}^{{\text{DPPH}}^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}}}$ (0.183–0.333 mg/ml), and ${\text{IC}}_{50}^{{\text{O}}_2^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}-}}$ (0.198–1.000 mg/ml) were calculated. The regression analysis produced moderate to high correlation coefficients between the scavenging activities and phenolics, and some individual phenolic compounds which indicated that beetroot pomace may be used as functional food ingredient. Cell growth effects were determined in MCF7 and MRC-5 cell lines, using SRB assay. IC₅₀ values were in the range of 362.478–503.525 and 383–587.880 μg/ml in MRC-5 and MCF7, respectively.