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"Bubblegum" acyl-CoA synthetase (ACSBG1) is a pivotal player in lipid metabolism during mouse brain development, facilitating the activation of long-chain fatty acids (LCFA) and their incorporation into lipid species that are crucial for brain function. ACSBG1 converts LCFA into acyl-CoA derivatives, supporting vital metabolic processes. Fruit fly mutants lacking ACSBG1 exhibited neurodegeneration and had elevated levels of very long-chain fatty acids (VLCFA), characteristics of human X-linked adrenoleukodystrophy (XALD). To explore ACSBG1's function and potential as a therapeutic target in XALD, we created an ACSBG1 knockout (Acsbg1−/−) mouse and examined the effects on brain FA metabolism during development. Phenotypically, Acsbg1−/− mice resembled wild type (w.t.) mice. ACSBG1 expression was found mainly in tissue affected pathologically in XALD, namely the brain, adrenal gland and testis. ACSBG1 depletion did not significantly reduce the total ACS enzyme activity in these tissue types. In adult mouse brain, ACSBG1 expression was highest in the cerebellum; the low levels detected during the first week of life dramatically increased thereafter. Unexpectedly, lower, rather than higher, saturated VLCFA levels were found in cerebella from Acsbg1−/− vs. w.t. mice, especially after one week of age. Developmental changes in monounsaturated ω9 FA and polyunsaturated ω3 FA levels also differed between w.t. and Acsbg1−/− mice. ACSBG1 deficiency impacted the developmental expression of several cerebellar FA metabolism enzymes, including those required for the synthesis of ω3 polyunsaturated FA, precursors of bioactive signaling molecules like eicosanoids and docosanoids. These changes in membrane lipid FA composition likely affect membrane fluidity and may thus influence the body's response to inflammation. We conclude that, despite compelling circumstantial evidence, it is unlikely that ACSBG1 directly contributes to the pathology of XALD, decreasing its potential as a therapeutic target. Instead, the effects of ACSBG1 knockout on processes regulated by eicosanoids and/or docosanoids should be further investigated. [ABSTRACT FROM AUTHOR]

Debilitating neurodegenerative conditions with metabolic origins affect millions of individuals worldwide. Still, for most of these neurometabolic disorders there are neither cures nor disease-modifying therapies, and novel animal models are needed for elucidation of disease pathology and identification of potential therapeutic agents. To date, metabolic neurodegenerative disease has been modeled in animals with only limited success, in part because existing models constitute analyses of single mutants and have thus overlooked potential redundancy within metabolic gene pathways associated with disease. Here, we present the first analysis of a very-long-chain acyl-CoA synthetase (ACS) double mutant. We show that the Drosophila bubblegum (bgm) and double bubble (dbb) genes have overlapping functions, and that the consequences of double knockout of both bubblegum and double bubble in the fly brain are profound, affecting behavior and brain morphology, and providing the best paradigm to date for an animal model of adrenoleukodystrophy (ALD), a fatal childhood neurodegenerative disease associated with the accumulation of very-long-chain fatty acids. Using this more fully penetrant model of disease to interrogate brain morphology at the level of electron microscopy, we show that dysregulation of fatty acid metabolism via disruption of ACS function in vivo is causal of neurodegenerative pathologies that are evident in both neuronal cells and their supporting cell populations, and leads ultimately to lytic cell death in affected areas of the brain. Finally, in an extension of our model system to the study of human disease, we describe our identification of an individual with leukodystrophy who harbors a rare mutation in SLC27a6 (encoding a very-long-chain ACS), a human homolog of bgm and dbb.

Abstract This work makes an overview of the evolution of Tipitip bubblegum comics in Turkey, studying its impact on society especially on children for more than four decades. Besides its colourful and positive characteristics, Tipitip comics fostered optimism intertwined with wit tailor made for the Turkish audience at the time. Tipitip not only presented accessible visuals for its audience but also introduced rich content ranging from sports to opera, occupations to traffic, transmitting valuable visual information in each illustration. Tipitip, promoted as ‘your cheerful friend’, was not only a father figure but also an enthusiast, an adventurer and an inventor as he is seen in many roles, from a conductor to a waiter, from a scout to a drummer, which made these comics inclusive and modern. The Tipitip bubblegum comics, similar to their contemporaries, achieved more than just market success; they benefited their audience, especially children, by reaching even small towns and initiating literary engagement. [ABSTRACT FROM AUTHOR]

By consensus, the acyl-CoA synthetase (ACS) community, with the advice of the human and mouse genome nomenclature committees, has revised the nomenclature for the mammalian long-chain acyl-CoA synthetases. ACS is the family root name, and the human and mouse genes for the long-chain ACSs are termed ACSL1,3–6 and Acsl1,3–6, respectively. Splice variants of ACSL3, -4, -5, and -6 are cataloged.Suggestions for naming other family members and for the nonmammalian acyl-CoA synthetases are made.

For bubblegum, the tight interfacial adhesion between a sugarcoating and the inner gum base and the hardness of sugarcoating ensure its high performance. Inspired by bubblegum, epoxidized natural rubber/reduced graphene oxide/ferroferric oxide (ENR/rGO/Fe3O4: oENR) composites were prepared to simultaneously achieve robust mechanical and electrical properties. According to FTIR, Raman, XPS, SEM and TEM, the molecular chains on the surface of ENR particles interact with rGO to form N–C covalent and NH–O hydrogen bond interfacial interactions via a "hydrazine bridge", which was the same as the hard sugarcoating function in bubblegum. However, the molecular chains inside ENR particles were not crosslinked, and acted in a manner similar to that of the gum base in bubblegum. Remarkably, this bubblegum inspired structure offered efficient conducting pathways and enhancement for oENR. Consequently, the tensile strength of oENR with 4.71 wt% rGO content (oENR 4.71) was 12.7 MPa, a 20.5-fold increment compared with that for neat ENR. Ductility was not impacted by the presence of filler. Strikingly, oENR possessed superior electrical conductivity of 0.1 S/cm and EMI SE of 40.6 dB with 99.97% absorbance efficiency. It displayed a 35.3 Gauge factor at low strain with sensitivity suitable for magnetic switching. Potential applications in electromagnetic interference shielding (EMI) and stretchable sensors were apparent. A novel approach for significantly improving both electrical and mechanical properties of epoxidized natural rubber has been demonstrated. This should facilitate potential application in multifunctional electronics. [Display omitted] • Segregated oENR with strong interfacial interactions were in-situ prepared. • rGO act as crosslinking center to form interfacial linkage by hydrazine bridge. • Tensile strength of oENR 4.71 increase 20.5-folds without sacrificing ductility. • oENR possess a percolation threshold of 0.15 wt% and conductivity of 50 S/m. • oENR show applications in EMI shielding, stretchable sensor and magnetic switch. [ABSTRACT FROM AUTHOR]

Long-chain fatty acyl-coenzyme As (CoAs) are critical regulatory molecules and metabolic intermediates. The initial step in their synthesis is the activation of fatty acids by one of 13 long-chain acyl-CoA synthetase isoforms. These isoforms are regulated independently and have different tissue expression patterns and subcellular locations. Their acyl-CoA products regulate metabolic enzymes and signaling pathways, become oxidized to provide cellular energy, and are incorporated into acylated proteins and complex lipids such as triacylglycerol, phospholipids, and cholesterol esters. Their differing metabolic fates are determined by a network of proteins that channel the acyl-CoAs toward or away from specific metabolic pathways and serve as the basis for partitioning. This review evaluates the evidence for acyl-CoA partitioning by reviewing experimental data on proteins that are believed to contribute to acyl-CoA channeling, the metabolic consequences of loss of these proteins, and the potential role of maladaptive acyl-CoA partitioning in the pathogenesis of metabolic disease and carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Gonadotropin-regulated long chain fatty acid Acyl-CoA synthetase (GR-LACS), is a member of the LACS family that is regulated by gonadotropin in the rat Leydig cell (LC). Its mouse/human homologs, lipidosin/bubblegum, have been suggested to participate in X-linked adrenoleukodystrophy (X-ALD), an adreno/neurodegenerative disorder with accumulation of very long chain fatty acids (VLCFA) in tissues and plasma. To further gain insights into its regulatory function, a GR-LACS/lipidosin null mouse was generated. No apparent phenotypic abnormalities were observed in the X-ALD target tissues (brain, testis, adrenal). Nuclear inclusions seen in mice >15 month-old, were present in LC of 9 month-old GR-LACS−/− mice. LC of the null mice showed refractoriness to the gonadotropin-induced desensitization of testosterone production that is observed in adult animals. LCFAs were moderately increased in the testis, ovary and brain, but not in the adrenal gland of GR-LACS−/− mice, with no major changes in VLCFA. No change in LACS activity was observed in these tissues, suggesting a compensatory mechanism exhibited by other LACS members. The GR-LACS−/− model did not support its association with X-ALD. These studies revealed a role of GR-LACS in reducing the aging process of the LC, and its participation in gonadotropin-induced testicular desensitization of testosterone production. [Copyright &y& Elsevier]

The principal biochemical abnormality in the neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD) is elevated plasma and tissue levels of very long-chain fatty acids (VLCFA). Enzymes with very long-chain acyl-CoA synthetase (VLACS) activity are required for VLCFA metabolism, including degradation by peroxisomal β-oxidation or incorporation into complex lipids, and may also participate in VLCFA synthesis. Two enzymes with VLACS activity, ACSVL1 and BG1, were investigated for their potential role in X-ALD biochemical pathology. Skin fibroblast mRNA levels for ACSVL1, an enzyme previously shown to be in peroxisomes and to participate in VLCFA β-oxidation, were not significantly different between normal controls, patients with childhood cerebral X-ALD, and patients with adrenomyeloneuropathy. Similar results were obtained with mRNA for BG1, a non-peroxisomal enzyme that is highly expressed in nervous system, adrenal gland, and testis, the principal tissues pathologically affected in X-ALD. No significant differences in the immunohistochemical staining patterns of tissues expressing either ACSVL1 or BG1 were observed when wild-type and X-ALD mice were compared. Western blot analysis of BG1 protein levels showed no differences between fibroblasts from controls, cerebral X-ALD, or adrenomyeloneuropathy patients. BG1 protein levels were similar in wild-type and X-ALD mouse brain, spinal cord, testis, and adrenal gland. We hypothesized that one function of BG1 was to direct VLCFA into the cholesterol ester synthesis pathway. However, BG1 depletion in Neuro2a cells using RNA interference did not decrease incorporation of labeled VLCFA into cholesterol esters. We conclude that the role, if any, of ACSVL1 and BG1 in X-ALD biochemical pathology is indirect. [Copyright &y& Elsevier]