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The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function and, more recently, with cellular proliferation. Tafazzin, an acyltransferase with key functions in CL remodeling determining actual CL composition, affects mitochondrial oxidative phosphorylation. Here, we show that the CRISPR-Cas9 mediated knock-out of tafazzin (Taz) is associated with substantial alterations of various mitochondrial and cellular characteristics in C6 glioma cells. The knock-out of tafazzin substantially changed the profile of fatty acids incorporated in CL and the distribution of molecular CL species. Taz knock-out was further associated with decreased capacity of oxidative phosphorylation that mainly originates from impaired complex I associated energy metabolism in C6 glioma cells. The lack of tafazzin switched energy metabolism from oxidative phosphorylation to glycolysis indicated by lower respiration rates, membrane potential and higher levels of mitochondria-derived reactive oxygen species but keeping the cellular ATP content unchanged. The impact of tafazzin on mitochondria was also indicated by altered morphology and arrangement in tafazzin deficient C6 glioma cells. In the cells we observed tafazzin-dependent changes in the distribution of cellular fatty acids as an indication of altered lipid metabolism as well as in stability/morphology. Most impressive is the dramatic reduction in cell proliferation in tafazzin deficient C6 glioma cells that is not mediated by reactive oxygen species. Our data clearly indicate that defects in CL phospholipid remodeling trigger a cascade of events including modifications in CL linked to subsequent alterations in mitochondrial and cellular functions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function, and cell proliferation. Changes in CL are often paralleled by changes in the lipid environment of mitochondria that may contribute to mitochondrial function and proliferation. This study aimed to separate the effects of CL content and CL composition from cellular free fatty acid distribution on bioenergetics and proliferation in C6 glioma cells. To this end, cardiolipin synthase and the CL remodelling enzyme, tafazzin, were knocked-down by siRNA in C6 cells. After 72 h of cultivation, we analysed CL composition by means of LC/MS/MS, distribution of cellular fatty acids by means of gas chromatography, and determined oxygen consumption and proliferation. Knock-down of cardiolipin synthase affected the cellular CL content in the presence of linoleic acid (LA) in the culture medium. Knock-down of tafazzin had no consequence with respect to the pattern of cellular fatty acids but caused a decrease in cell proliferation. It significantly changed the distribution of molecular CL species, increased CL content, decreased oxygen consumption, and decreased cell proliferation when cultured in the presence of linoleic acid (LA). The addition of linoleic acid to the culture medium caused significant changes in the pattern of cellular fatty acids and the composition of molecular CL species. These data suggest that tafazzin is required for efficient bioenergetics and for proliferation of glioma cells. Supplementation of fatty acids can be a powerful tool to direct specific changes in these parameters., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The angiotensin-converting enzyme 2/angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system often opposes the detrimental effects of the angiotensin-converting enzyme/Ang II/Ang II type 1 receptor axis and has been associated with beneficial effects on glucose homeostasis, whereas underlying mechanisms are mostly unknown. Here we investigate the effects of Ang-(1-7) and its receptor Mas on β-cell function. Isolated islets from Mas-deficient and wild-type mice were stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion determined. Islets' cytoplasmic calcium and cAMP concentrations, mRNA amounts of Ins1, Ins2, Pdx1, and Mafa and effects of inhibitors of cAMP downstream signaling were determined. Ang-(1-7) was also applied to mice by osmotic pumps for 14 days and effects on glucose tolerance and insulin secretion were assessed. Ang-(1-7) increased insulin secretion from wild-type islets, whereas antagonists and genetic Mas deficiency led to reduced insulin secretion. The Mas-dependent effects of Ang-(1-7) on insulin secretion did not result from changes in insulin gene expression or changes in the excitation-secretion coupling but from increased intracellular cAMP involving exchange protein activated directly by cAMP. Administration of Ang-(1-7) in vivo had only marginal effects on glucose tolerance in wild-type mice but still resulted in improved insulin secretion from islets isolated of these mice. Interestingly, although less pronounced than in wild types, Ang-(1-7) still affected insulin secretion in Mas-deficient islets. The data indicate a significant function of Ang-(1-7) in the regulation of insulin secretion from mouse islets in vitro and in vivo, mainly, but not exclusively, by Mas-dependent signaling, modulating the accessory pathway of insulin secretion via increase in cAMP.

NGOs are actively using social networks, especially Instagram, to disseminate audiovisual content with a strong emotional response and to achieve effective and participatory communication that contributes to greater awareness and social mobilisation. A recurring and interesting focus of their campaigns is the situation of migrant minors, a vulnerable group that is often ignored and dehumanised. The aim of this work is to identify and highlight good practices of Spanish NGOs, a sensitive border area and the main gateway to Europe, so that they can be replicated in other geographical contexts to promote social change. [ABSTRACT FROM AUTHOR]

Hemispheric asymmetry is known for higher brain functions like language and attention. We tested whether such an asymmetry also exists in the representation of elementary sensory functions. Magnetic source imaging was used to compare the cortical somatosensory hand representation in seven right- and five left-handed individuals. In all right-handers the representation of the dominant hand was larger than the contralateral one in the corresponding hemispheres. In contrast, only two out of five left-handers revealed a larger representation of the dominant left hand compared to the right one. In agreement with previous findings on the lateralization of language and attention, there is a strong correlation between handedness and the extent of the cortical hand representation in right-, but not in left-handers. We conclude that a profound functional hemispheric asymmetry also exists in primary sensory cortices.

A new variation of the Reformatzy reaction with use of I2/zinc and chlorotrimethylsilane in THF and a shortened work-up is described allowing the synthesis of a wide variety of substituted beta-lactams 3 in fairly good yield. These lactams are silylated according to the Peterson reaction yielding by reactions with appropriate carbonyl compounds E/Z-mixturs of the substituted 3-methylidene beta-lactams 7, 8 and 10. The isomers are separated by CC and completely characterized by spectroscopic methods, mainly 1H NMR spectroscopy. Condensation of the 3-formyl methylidene derivative 10 with amines or malonate yields the conjugated products 11, and from the isopropylidene derivative 6 the pyridinium sulfonate 14 is prepared via 12 and 13. All methylidene beta-lactams are prepared as model compounds for studying their activity against beta-lactamases and for elucidating the mechanism of action.

Breeding for higher fertility has resulted in a higher number of low birthweight (LBW) piglets. It has been shown that LBW piglets grow slower than normal birthweight (NBW) littermates. Differences in growth performance have been associated with impaired small intestinal development. In suckling and weaning piglets, glutamine (Gln) supplementation has been associated with improved growth and intestinal development. This study was designed to examine the effects of oral Gln supplementation on growth and small intestinal parameters in LBW and NBW suckling piglets. At birth (day 0), a total of 72 LBW (1.10 ± 0.06 kg) and 72 NBW (1.51 ± 0.06) male piglets were selected. At day 1, litters were standardized to 12 piglets, and experimental piglets supplemented daily with either Gln (1 g/kg BW) or isonitrogenous amounts of Alanine (Ala) as control (1.22 g/kg BW) until day 12. Creep feed was offered from day 14 onward. Subgroups of piglets were euthanized at days 5, 12, and 26 for the analyses of jejunal morphometry, cellular proliferation, glutathione concentration and transcript abundance of tight junction proteins. From age day 11 to 21, Gln supplemented LBW (LBW-Gln) piglets were heavier than Ala supplemented LBW (LBW-Ala) littermates (P = 0.034), while NBW piglets were heavier until age day 26 compared to LBW littermates. Villus height was higher in LBW-Gln compared to LBW-Ala on age day 12 (P = 0.031). Sporadic differences among supplementation and birthweight groups were detected for jejunal cellular proliferation, cellular population and glutathione concentration, whereas age was the most dominant factor. These results show that Gln supplementation improved the growth of LBW piglets compared to LBW-Ala beyond the termination of Gln supplementation, but this was not associated with consistent effects on selected parameters of jejunal development. [ABSTRACT FROM AUTHOR]

Purpose: Writing a thesis is a difficult endeavor for undergraduate students, especially in management careers, due to the highly practical approach of the discipline. Students often find difficult to understand and apply research methods in concrete research projects, so a proper set of teaching-learning strategies is critical. This study aimed to examine the effect of these strategies on the academic performance of students in two research seminars in an undergraduate management program in Peru. Design/methodology/approach: The research adopted a mixed approach. The quantitative component included a survey of 249 students in both seminars, while the qualitative one involved only some of the students using three focus groups. The corresponding data analysis included stepwise linear regression models and content analysis. Findings: The study found that a clear course structure, adequate research methods literature, good advisor–student communication and goal planning and achievement were the key determinants of the students' final grades. Originality/value: This research fills a gap in previous studies on the subject by including a broader set of strategies and by statistically estimating the strategies' effects on academic performance. [ABSTRACT FROM AUTHOR]

Timely detection of underground natural gas leakage is significant for the safe production of gas storage and the protection of ecological environment. Direct detection makes it difficult to identify natural gas micro-leakage accurately, while hyperspectral remote sensing can identify micro-leakage based on spectral changes of vegetation near the leakage area. However, the spectral morphological characteristics of vegetation leaves under natural gas micro-leakage will undergo complex changes over time, making it difficult to identify vegetation stress. Temporal spectral characteristics improve the capability of capturing spectral differences of stressed vegetation at different times, allowing for indirect evaluation of leaked information. This study simulates the stress of underground natural gas storage micro leaks on bean growth through field experiments. Based on the changes in spectral reflectance and chlorophyll content of leaves, temporal features were constructed based on multi-temporal reflectance data, and feature selection methods were used to obtain bands sensitive to natural gas stress. This paper proposed a leaf scale natural gas micro-leakage identification index based on temporal spectral features (TNII) to identify bean stress under natural gas leakage. The results are summarized as follows: (1) With the leakage of underground natural gas, the spectral reflectance of leaves increased in the visible and near-infrared range, and the chlorophyll content decreased. (2) The TNII (R 676 − R 526 ) T n − (R 676 − R 526 ) T 1 (R 676 − R 526 ) T n + (R 676 − R 526 ) T 1 constructed based on sensitive wavebands (676 and 526 nm) can be employed to identify bean stress under natural gas after 17 days of leakage. The JM (Jefferies Matusita) distance test indicates that TNII could timely and stably identify bean stress under natural gas micro-leakage (JM > 1.8). This study provides the theoretical basis and technology support for micro-leakage detection of underground gas storage or pipelines. [ABSTRACT FROM AUTHOR]

The review covers research published since 2017 and is focused on enantioselective synthesis using radical reactions. It describes recent approaches to the asymmetric synthesis of chiral molecules based on the application of the metal catalysis, dual metal and organocatalysis and finally, pure organocatalysis including enzyme catalysis. This review focuses on the synthetic aspects of the methodology and tries to show which compounds can be obtained in enantiomerically enriched forms. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic problem of the intestine and relapsing in nature. Biochanin A is a nature-derived isoflavonoid and has numerous bioactivities. However, its role against UC and intestinal inflammation remains obscure. We aimed to comprehensively explore the pharmacological effect of biochanin A in alleviating colitis and to evaluate the potential mechanisms. Initially, we explored the anti-inflammatory action of biochanin A (15, 30, and 60 μM) by employing lipopolysaccharide (LPS)-activated RAW 264.7 cells. In RAW 264.7 cells under LPS stimulation, biochanin A inhibited the elevation of reactive oxygen species (ROS) (p < 0.0001), interleukin (IL)-1β (p < 0.0001), IL-18 (p < 0.01), and tumor necrosis factor (TNF)-α (p < 0.01) release, nitrite production (p < 0.0001), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Next, we studied the effectiveness of biochanin A (20 and 40 mg/kg) in mouse colitis induced with dextran sulfate sodium (DSS) by assessing colon length, disease activity index (DAI) scoring, and performing colonoscopy and histological analysis. The pro-inflammatory cytokines were estimated using ELISA. Western blot studies were performed to assess underlying mechanisms. In mice, biochanin A treatment alleviated DAI score (p < 0.0001), restored colon length (p < 0.05) and morphology, and re-established colon histopathology. Biochanin A affects the phosphorylation of proteins associated with NF-κB (p65) and mitogen-activated protein kinase (MAPK) axis and regulates colonic inflammation by reducing the expression of inflammatory cytokines and myeloperoxidase (MPO) activity. Altogether, our findings support the idea that the anticolitis potential of biochanin A is allied with anti-inflammatory activity by inhibiting the MAPK/NF-κB (p65) axis. Hence, biochanin A may be an alternative option to alleviate the risk of colitis., (© 2024 Wiley Periodicals LLC.)

We describe convenient preparations of N,N′‐dialkyl‐1,3‐propanedialdiminium chlorides, N,N′‐dialkyl‐1,3‐propanedialdimines, and lithium N,N′‐dialkyl‐1,3‐propanedialdiminates in which the alkyl groups are methyl, ethyl, isopropyl, or tert‐butyl. For the dialdiminium salts, the N2C3 backbone is always in the trans‐s‐trans configuration. Three isomers are present in solution except for the tert‐butyl compound, for which only two isomers are present; increasing the steric bulk of the N‐alkyl substituents shifts the equilibrium away from the (Z,Z) isomer in favor of the (E,Z), and (E,E) isomers. For the neutral dialdimines, crystal structures show that the methyl and isopropyl compounds adopt the (E,Z) form, whereas the tert‐butyl compound is in the (E,E) form. In aprotic solvents all four dialdimines (as well as the lithium dialdiminate salts) adopt cis‐s‐cis conformations in which there presumably is either an intramolecular hydrogen bond (or a lithium cation) between the two nitrogen atoms. [ABSTRACT FROM AUTHOR]

Simple Summary: This review discusses the synthesis and significance of fatty acids, glycerophospholipids, and triacylglycerol in glioblastoma. The focus is on all enzymes involved in the synthesis of these lipids, highlighting their roles in the tumorigenesis of glioblastoma. Due to the fact that the role of many of these enzymes in glioblastoma tumorigenesis remains unexplored, we conducted a bioinformatic analysis based on the GEPIA database to indicate their possible functions and significance. Specific properties of certain enzymes were also described to indicate their functions in the tumorigenesis of glioblastoma better. One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR). [ABSTRACT FROM AUTHOR]