TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A

The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer and has a role in metabolic rewiring during tumor development. However, little is known about the role of this enzyme in proliferative tissues under physiological conditions. In the current work, we analysed the role of TIGAR in primary human lymphocytes stimulated with the mitotic agent Concanavalin A (ConA). We found that TIGAR expression was induced in stimulated lymphocytes through the PI3K/AKT pathway, since Akti-1/2 and LY294002 inhibitors prevented the upregulation of TIGAR in response to ConA. In addition, suppression of TIGAR expression by siRNA decreased the levels of the proliferative marker PCNA and increased cellular ROS levels. In this model, TIGAR was found to support the activity of glucose 6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentose phosphate pathway (PPP), since the inhibition of TIGAR reduced G6PDH activity and increased autophagy. In conclusion, we demonstrate here that TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, which contributes to the redirection of the carbon flux to the PPP.     

Power‐efficient analog design based on the class AB super source follower

A class AB version of the conventional super source follower (SSF) is described. The circuit greatly increases slew rate (SR) and current efficiency, maintaining the low distortion and low output resistance of the SSF. Class AB operation is achieved without extra power dissipation or supply requirements, and without bandwidth or noise degradation. The circuit can advantageously replace the SSF in a wide variety of analog systems, opening a new research line in analog design. To illustrate the widespread application of this cell, a class AB differential unity‐gain buffer, a class AB differential current mirror and two class AB differential transconductors are designed, fabricated in a 0.5µm CMOS technology and tested. Measurement results using a dual supply of ±1.65V show that the proposed class AB version of the SSF improves SR by a factor 21.5 and increases bandwidth by 10%, keeping noise level, input range, power consumption, and supply requirements unaltered. The fabricated class AB current mirror features a THD at 100 kHz of ? 62dB for signal currents 20 times larger than the bias current. The fabricated transconductors feature an IM3 at 1 MHz of ? 56.6dB for output currents more than 13 times larger than the bias currents. Copyright © 2011 John Wiley & Sons, Ltd.     

Highly Diastereo‐ and Enantioselective Catalytic Domino Thia‐Michael/Aldol Reactions: Synthesis of Benzothiopyrans with Three Contiguous Stereocenters

Highly enantioselective organocatalytic domino thia‐Michael/aldol reactions between 2‐mercaptoacetophenone and α,β‐unsaturated aldehydes are presented. The reactions proceed with excellent chemo‐, diastereo‐ and enantioselectivity to give the corresponding benzothiopyran derivatives in high yields with up to >15:1 dr and 96 to >99 % ee.     

Identification of potential technologies for 1,4-Butanediol production using prospecting methodology

1,4-Butanediol (1,4-BDO) is a four-carbon diol used for industrial applications such as organic solvents, and the production of adhesives, fibers and polyurethanes. 1,4-BDO currently is produced through several petrochemical routes: hydrogenation of maleic anhydride, isomerization of propylene oxide, acetoxylation of butadiene, and the reaction between formaldehyde and acetylene. The current trends in 1,4-BDO production involve the utilization of renewable sources such as biomass. In this context, the present study aimed to identify promising technologies of 1,4-BDO production through prospecting methodology based on the analyses of patents and scientific article, describing the most relevant aspects of those emerging technologies. An increasing amount of 1,4-BDO production focused on biotechnological routes has been reported, with the US heavily involved in the development of new technologies. This study tracked three promising technologies which have potential for application in a biorefinery context because those processes involve (i) production of 1,4-BDO from sugars, classified herein as the biotechnological route; (ii) production of intermediates from sugar fermentation followed by catalytic conversion into 1,4-BDO, classified herein as the hybrid route, and (iii) furan/furfural conversion into 1,4-BDO. © 2020 Society of Chemical Industry     

Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death

A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death.     

Bewirtschaftungsmaßnahmen zur Reduzierung der Nitratbelastung im Einzugsgebiet der Quellfassung Schleinitz

Grundwasser - Im Untersuchungsgebiet Schleinitz führte eine Grünlandumnutzung einer ehemaligen Ackerfläche über einen Zeitraum von annähernd 6 Jahren zu einer...     

Aggregation Behavior,Antibacterial Activity and Biocompatibility of Catanionic Assemblies Based on Amino Acid-Derived Surfactants

The surface activity, aggregates morphology, size and charge characteristics of binary catanionic mixtures containing a cationic amino acid-derived surfactant N(π), N(τ)-bis(methyl)-L-Histidine tetradecyl amide (DMHNHC₁₄) and an anionic surfactant (the lysine-based surfactant N^α-lauroyl-N^εacetyl lysine (C₁₂C₃L) or sodium myristate) were investigated for the first time. The cationic surfactant has an acid proton which shows a strong pK_a shift irrespective of aggregation. The resulting catanionic mixtures exhibited high surface activity and low critical aggregation concentration as compared with the pure constituents. Catanionic vesicles based on DMHNHC₁₄/sodium myristate showed a monodisperse population of medium-size aggregates and good storage stability. According to Small-Angle X-Ray Scattering (SAXS), the characteristics of the bilayers did not depend strongly on the system composition for the positively charged vesicles. Negatively charged vesicles (cationic surfactant:myristate ratio below 1:2) had similar bilayer composition but tended to aggregate. The DMHNHC₁₄-rich vesicles exhibited good antibacterial activity against Gram-positive bacteria and their bactericidal effectivity declined with the decrease of the cationic surfactant content in the mixtures. The hemolytic activity and cytotoxicity of these catanionic formulations against non-tumoral (3T3, HaCaT) and tumoral (HeLa, A431) cell lines also improved by increasing the ratio of cationic surfactant in the mixture. These results indicate that the biological activity of these systems is mainly governed by the cationic charge density, which can be modulated by changing the cationic/anionic surfactant ratio in the mixtures. Remarkably, the incorporation of cholesterol in those catanionic vesicles reduces their cytotoxicity and increases the safety of future biomedical applications of these systems.