Proteomic Profiling of Astrocytic O-GlcNAc Transferase-Related Proteins in the Medial Prefrontal Cortex

The medial prefrontal cortex (mPFC), a key part of the brain networks that are closely related to the regulation of behavior, acts as a key regulator in emotion, social cognition, and decision making. Astrocytes are the majority cell type of glial cells, which play a significant role in a number of processes and establish a suitable environment for the functioning of neurons, including the brain energy metabolism. Astrocyte’s dysfunction in the mPFC has been implicated in various neuropsychiatric disorders. Glucose is a major energy source in the brain. In glucose metabolism, part of glucose is used to convert UDP-GlcNAc as a donor molecule for O-GlcNAcylation, which is controlled by a group of enzymes, O-GlcNAc transferase enzyme (OGT), and O-GlcNAcase (OGA). However, the role of O-GlcNAcylation in astrocytes is almost completely unknown. Our research showed that astrocytic OGT could influence the expression of proteins in the mPFC. Most of these altered proteins participate in metabolic processes, transferase activity, and biosynthetic processes. GFAP, an astrocyte maker, was increased after OGT deletion. These results provide a framework for further study on the role of astrocytic OGT/O-GlcNAcylation in the mPFC.

Lipid and fatty acid metabolism in trypanosomatids

Trypanosomiases and leishmaniases are neglected tropical diseases that have been spreading to previously non-affected areas in recent years. Identification of new chemotherapeutics is needed as there are no vaccines and the currently available treatment options are highly toxic and often ineffective. The causative agents for these diseases are the protozoan parasites of the Trypanosomatidae family, and they alternate between invertebrate and vertebrate hosts during their life cycles. Hence, these parasites must be able to adapt to different environments and compete with their hosts for several essential compounds, such as amino acids, vitamins, ions, carbohydrates, and lipids. Among these nutrients, lipids and fatty acids (FAs) are essential for parasite survival. Trypanosomatids require massive amounts of FAs, and they can either synthesize FAs de novo or scavenge them from the host. Moreover, FAs are the major energy source during specific life cycle stages of T. brucei, T. cruzi, and Leishmania. Therefore, considering the distinctive features of FAs metabolism in trypanosomatids, these pathways could be exploited for the development of novel antiparasitic drugs. In this review, we highlight specific aspects of lipid and FA metabolism in the protozoan parasites T. brucei, T. cruzi, and Leishmania spp., as well as the pathways that have been explored for the development of new chemotherapies.

Embryonic steroids control developmental programming of energy balance

Glucose is a major energy source for growth. At birth, neonates must change their energy source from maternal supply to its own glucose production. The mechanism of this transition has not been clearly elucidated. To evaluate the possible roles of steroids in this transition, here we examine the defects associated with energy production of a mouse line that cannot synthesize steroids de novo due to the disruption of its Cyp11a1 gene. The Cyp11a1 null embryos had insufficient blood insulin, and failed to store glycogen in the liver since embryonic day 16.5. Their blood glucose dropped soon after maternal deprivation, and the expression of hepatic gluconeogenic and glycogenic genes were reduced. Insulin was synthesized in the mutant fetal pancreas, but failed to be secreted. Maternal glucocorticoid supply rescued the amounts of blood glucose, insulin, and liver glycogen in the fetus, but did not restore expression of genes for glycogen synthesis, indicating the requirement of de novo glucocorticoid synthesis for glycogen storage. Thus, our investigation of Cyp11a1 null embryos reveals that the energy homeostasis is established before birth, and fetal steroids are required for the regulation of glycogen synthesis, hepatic gluconeogenesis and insulin secretion at the fetal stage.

A Novel Concept for Sustainable Food Production Utilizing Low Temperature Industrial Surplus Heat

Low temperature industrial surplus heat represents a major energy source that is currently only rarely utilized due to its low quality. An agricluster allows for the leveraging of this low-quality heat and, hence, may improve the overall energy efficiency. This paper presents the novel concept of an agricluster driven by available surplus heat from industrial processes. We propose the integration of greenhouse production, insect rearing, fish rearing, and drying of seaweed using low temperature surplus heat from the aluminum industry. Each of these processes is already used in or investigated for utilization of surplus heat and partly coupled with other processes, such as in aquaponics. However, the integration of all processes in an agricluster—as proposed in this paper—may result in improved utilization of the surplus heat due to the different seasonality of the heat demand. The potential synergies of this integration approach are discussed in this paper. Furthermore, waste from one process can be utilized as an input stream to other processes, reducing the demand for external material input to the system. The proposed concept of an agricluster is especially interesting for the Nordic countries, as they are dependant on fresh food imports due to the low outside temperatures.

Exploiting Microbes in the Petroleum Field: Analyzing the Credibility of Microbial Enhanced Oil Recovery (MEOR)

Crude oil is a major energy source that is exploited globally to achieve economic growth. To meet the growing demands for oil, in an environment of stringent environmental regulations and economic and technical pressure, industries have been required to develop novel oil salvaging techniques. The remaining ~70% of the world’s conventional oil (one-third of the available total petroleum) is trapped in depleted and marginal reservoirs, and could thus be potentially recovered and used. The only means of extracting this oil is via microbial enhanced oil recovery (MEOR). This tertiary oil recovery method employs indigenous microorganisms and their metabolic products to enhance oil mobilization. Although a significant amount of research has been undertaken on MEOR, the absence of convincing evidence has contributed to the petroleum industry’s low interest, as evidenced by the issuance of 400+ patents on MEOR that have not been accepted by this sector. The majority of the world’s MEOR field trials are briefly described in this review. However, the presented research fails to provide valid verification that the microbial system has the potential to address the identified constraints. Rather than promising certainty, MEOR will persist as an unverified concept unless further research and investigations are carried out.

Glucose Metabolism: The Metabolic Signature of Tumor Associated Macrophage

Macrophages exist in most tissues of the body, where they perform various functions at the same time equilibrating with other cells to maintain immune responses in numerous diseases including cancer. Recently, emerging investigations revealed that metabolism profiles control macrophage phenotypes and functions, and in turn, polarization can trigger metabolic shifts in macrophages. Those findings implicate a special role of metabolism in tumor-associated macrophages (TAMs) because of the sophisticated microenvironment in cancer. Glucose is the major energy source of cells, especially for TAMs. However, the complicated association between TAMs and their glucose metabolism is still unclearly illustrated. Here, we review the recent advances in macrophage and glucose metabolism within the tumor microenvironment, and the significant transformations that occur in TAMs during the tumor progression. Additionally, we have also outlined the potential implications for macrophage-based therapies in cancer targeting TAMs.

Effect of Symmetrically Switched Rectifier Topologies on the Frequency Regulation of Standalone Micro-Hydro Power Plants

Micro-hydro power plants (μHPPs) are a major energy source in grid-isolated zones because they do not require reservoirs and dams to be built. μHPPs operate in a standalone mode, but a continuously varying load generates voltage unbalances and frequency fluctuations which can cause long-term damage to plant components. One method of frequency regulation is the use of alternating current-alternating current (AC-AC) converters as an electronic load controller (ELC). The disadvantage of AC-AC converters is reactive power consumption with the associated decrease in both the power factor and the capacity of the alternator to deliver current. To avoid this disadvantage, we proposed two rectifier topologies combined with symmetrical switching. However, the performance of the frequency regulation loop with each topology remains unknown. Therefore, the objective of this work was to evaluate the performance of the frequency regulation loop when each topology, with a symmetrical switching form, was inserted. A MATLAB® model was implemented to simulate the frequency loop. The results from a μHPP case study in a small Cuban rural community called ‘Los Gallegos’ showed that the performance of the frequency regulation loop using the proposed topologies satisfied the standard frequency regulation and increased both the power factor and current delivery capabilities of the alternator.

Total and Sn-2 Fatty Acid Profile in Human Colostrum and Mature Breast Milk of Women Living in Inland and Coastal Areas of China

Introduction: Although lipid is the major energy source and exerts beneficial effects on infant growth, research on the composition of fatty acid (FA) at the sn-2 position of human milk (HM) in China and abroad is limited. Objectives: This study aimed to investigate the FA positional distribution in colostrum and mature HM of women living in the inland and coastal areas of China and explore the potential influences of geographical region and lactation stage on the FA profile of Chinese women. Methods: Colostrum milk (n = 61) and mature milk (n = 56) samples were obtained longitudinally from healthy lactating women in Guangzhou and Chengdu, China. Gas chromatography was used to determine the total and sn-2 FA composition. Results: Significant differences were observed in the FA profile of HM between different regions and lactation stages, with differences in polyunsaturated FA levels being the most pronounced. Nearly 70% of sn-2 FAs were saturated FAs, of which C16:0 accounted for approximately 75%. C8:0, C10:0, C18:0, C20:0, C22:0, and all of the unsaturated FAs were mainly located at the sn-1 and sn-3 positions, while C14:0, C15:0, and C16:0 were mainly at the sn-2 position. The proportion of C12:0 and C17:0 at sn-2 was approximately equivalent to that at the sn-1, 3 positions. Conclusions: The results indicate the variability in the FA profile of HM between regions and lactation stages. The contents of polyunsaturated FAs and sn-2 FAs, especially palmitic acid, should be paid more attention when optimizing infant formula.

Bacterial F-type ATP synthases follow a well-choreographed assembly pathway

F-type ATP synthases are multiprotein complexes composed of two separate coupled motors (F1 and FO) generating adenosine triphosphate (ATP) as the universal major energy source in a variety of relevant biological processes in mitochondria, bacteria and chloroplasts. In the past decades, ATP synthases have become a subject of high interest, as a target for therapeutic use in the treatment of a variety of diseases. While the structure of many ATPases is solved today, the precise assembly pathway of F1FO-ATP synthases is mostly still unclear. To probe the bacterial F1 assembly of Acetobacterium woodii, we studied the self-assembly of purified proteins under different environments. We report assembly requirements, important assembly intermediates in vitro and in vivo, the crucial role of nucleotide binding (as opposed to ATP hydrolysis) and correlate results with complex activity. Finally, we propose a model for the assembly pathway for the formation of a functional F1 complex.

LDH-A Knockdown: Changes in The LDH Isoenzyme Profile and Variability in Glioma Response

Background: Lactate metabolism in tumors is now recognized as a major energy source and a major gluconeogenic precursor for many tumors, as well as shown to exhibit signaling properties. There is less information on the role of the LDH/lactate axis in brain tumors, although lactate formation in gliomas is associated with poor survival. Methods: Three murine glioma cell lines (GL261, CT2A, and ALTS1C1) were transduced to knockdown (KD) expression of the murine LDH-A gene. The effects of the LDH-A KD were compared to those in control (NC) cells and tumors. Results: Differences in the expression of LDH-A and LDH-B mRNA, protein, and enzymatic activity were observed in the six cell lines. LDH zymography showed a major difference in LDH subunit distribution between GL261 LDH-A KD and NC tumors, whereas little or no effect of LDH-A KD was observed in CT2A and ALTS1C1 tumors. Tumors LDH-A and LDH-B immunohistochemistry and a Weka segmentation analysis were consistent with isoenzyme patterns and the above analyses. An “inverse” LDH-A/LDH-B staining relationship (high vs low) was observed in many local GL261 tumor regions. In contrast, CT2A tumors showed a more “direct” local LDH-A/LDH-B staining relationship. LDH-A KD prolonged the doubling time of GL261 cells in culture and prevented the formation of subcutaneous flank tumors in immune-competent C57BL/6 mice (GL261 NC tumors had a prolonged growth delay). In nude mice, both LDH-A KD and NC GL261 tumors grew more rapidly than GL261 NC tumors in C57BL/6 mice. No differences between NC and KD cell proliferation (in vitro) and tumor growth in C57BL/6 mice (doubling time) were observed for CT2A and ALTS1C1 cells and tumors, consistent with the absence of a difference in their LDH isoenzyme profiles. Conclusions: These results show the combined impact of a genetic alteration (LDH-A depletion) on the LDH isoenzyme profile, expression of LDH-A vs LDH-B and LDH enzymatic activity, and the immune system (C57BL/6 vs nude mice) on the growth of s.c. located tumors.