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Leif Hertz, M.D., D.Sc. (honōris causā) (1930-2018), was one of the original and noteworthy participants in the International Conference on Brain Energy Metabolism (ICBEM) series since its inception in 1993. The biennial ICBEM conferences are organized by neuroscientists interested in energetics and metabolism underlying neural functions; they have had a high impact on conceptual and experimental advances in these fields and on promoting collaborative interactions among neuroscientists. Leif made major contributions to ICBEM discussions and understanding of metabolic and signaling characteristics of astrocytes and their roles in brain function. His studies ranged from uptake of K + from extracellular fluid and its stimulation of astrocytic respiration, identification, and regulation of enzymes specifically or preferentially expressed in astrocytes in the glutamate-glutamine cycle of excitatory neurotransmission, a requirement for astrocytic glycogenolysis for fueling K + uptake, involvement of glycogen in memory consolidation in the chick, and pharmacology of astrocytes. This tribute to Leif Hertz highlights his major discoveries, the high impact of his work on astrocyte-neuron interactions, and his unparalleled influence on understanding the cellular basis of brain energy metabolism. His work over six decades has helped integrate the roles of astrocytes into neurotransmission where oxidative and glycogenolytic metabolism during neurotransmitter glutamate turnover are key aspects of astrocytic energetics. Leif recognized that brain astrocytic metabolism is greatly underestimated unless the volume fraction of astrocytes is taken into account. Adjustment for pathway rates expressed per gram tissue for volume fraction indicates that astrocytes have much higher oxidative rates than neurons and astrocytic glycogen concentrations and glycogenolytic rates during sensory stimulation in vivo are similar to those in resting and exercising muscle, respectively. These novel insights are typical of Leif's astute contributions to the energy metabolism field, and his publications have identified unresolved topics that provide the neuroscience community with challenges and opportunities for future research., (© 2023 International Society for Neurochemistry.)

Isotopic assays of brain glucose utilization rates have been used for more than four decades to establish relationships between energetics, functional activity, and neurotransmitter cycling. Limitations of these methods include the relatively long time (1-60 min) for the determination of labeled metabolite levels and the lack of cellular resolution. Identification and quantification of fuels for neurons and astrocytes that support activation and higher brain functions are a major, unresolved issues. Glycolysis is preferentially up-regulated during activation even though oxygen level and supply are adequate, causing lactate concentrations to quickly rise during alerting, sensory processing, cognitive tasks, and memory consolidation. However, the fate of lactate (rapid release from brain or cell-cell shuttling coupled with local oxidation) is long disputed. Genetically encoded biosensors can determine intracellular metabolite concentrations and report real-time lactate level responses to sensory, behavioral, and biochemical challenges at the cellular level. Kinetics and time courses of cellular lactate concentration changes are informative, but accurate biosensor calibration is required for quantitative comparisons of lactate levels in astrocytes and neurons. An in vivo calibration procedure for the Laconic lactate biosensor involves intracellular lactate depletion by intravenous pyruvate-mediated trans-acceleration of lactate efflux followed by sensor saturation by intravenous infusion of high doses of lactate plus ammonium chloride. In the present paper, the validity of this procedure is questioned because rapid lactate-pyruvate interconversion in blood, preferential neuronal oxidation of both monocarboxylates, on-going glycolytic metabolism, and cellular volumes were not taken into account. Calibration pitfalls for the Laconic lactate biosensor also apply to other metabolite biosensors that are standardized in vivo by infusion of substrates that can be metabolized in peripheral tissues. We discuss how technical shortcomings negate the conclusion that Laconic sensor calibrations support the existence of an in vivo astrocyte-neuron lactate concentration gradient linked to lactate shuttling from astrocytes to neurons to fuel neuronal activity., (© 2023 International Society for Neurochemistry.)

The experiment aimed to investigate the effects of flaxseed lignans (SDG) on mammary gland development, lactation performance, and lactation-related hormone levels in primiparous rats. A total of 80 primiparous rats were randomly divided into four groups (20 rats per group). The control group was fed a normal diet, while the test groups I, II, and III were fed a normal diet plus orally administered 125 mg/(L⋅kg) SDG, 5 mg/(L⋅kg) Br, and 125 mg/(L⋅kg) SDG + 5 mg/(L⋅kg) Br, respectively. SDG was administered throughout pregnancy, and Br was given from the 14th day of gestation until delivery. Medication was stopped on the day of delivery, and eight pups from each litter were retained for milk production measurement. The experimental period lasted for 15 days. The results showed that the milk production on days 13 and 15 of groups I and III was significantly higher than that of group II (P<0.01 or P<0.05). The mammary gland weight, mammary DNA and RNA content, and the RNA/DNA ratio in test group I were significantly higher than those in the control group (P<0.05), and extremely higher than those in test group II (P<0.01). The acini diameter in the mammary glands of rats in test groups I and III was significantly higher than that in the control group and test group II (P<0.05), and the duct diameter was extremely higher than that in the control group and test groupII (P<0.01). The levels of reproductive axis hormones in group I were significantly higher than those in the other groups, with estradiol (E2) and prolactin (PRL) were significantly higher than those in test group II (P<0.05), and progesterone (P), follicle-stimulating hormone (FSH), and growth hormone (GH) were extremely higher than those in test group II (P<0.01). The study indicates that the administration of SDG can improve rat mammary function, promote the development of mammary acini and ducts, increase milk production, and elevate lactation-related hormone levels. The effects of different treatment groups on the mammary glands of primiparous rats were ranked as follows: Test group I > test group III > test control group > test group II. [ABSTRACT FROM AUTHOR]

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non-invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [ 15 O]H 2 O and [ 18 F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D 2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine-enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine-enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non-monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P 2 X 7 receptor, type 1 cannabinoid receptor (CB 1 ), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed., (© 2022 International Society for Neurochemistry.)

Global warming, water scarcity, population growth, rising food prices, urbanization, and other socio-economic factors pose significant threats to agriculture and food security in the 21st century. This situation is particularly grave for low-income individuals in the Asia-Pacific region. To tackle this challenge and eradicate hunger and poverty, it is imperative for scientists to explore alternative food sources, covering all stages from production through processing to consumption. Cereal grains serve as a crucial food source and hold substantial importance in human diets. Therefore, revamping the food system becomes crucial to achieve food and nutritional security. A pragmatic approach toward reaching this goal involves ensuring universal access to affordable, wholesome, and nourishing food through the utilization of millets—nutrient-dense grains (often referred to as Nutri-cereals) that offer a rich array of vital macronutrients, micronutrients, carbohydrates, protein, dietary fiber, lipids, and phytochemicals. Leveraging these grains holds the potential to significantly alleviate the challenges of food insecurity and malnutrition. Millet, a drought-resistant grain, constitutes a primary source of carbohydrates and proteins for populations residing in semi-arid regions of Africa and Asia. Given its crucial contribution to national food security and potential health advantages, there is a growing focus among food scientists. Additionally, the United Nations designated 2023 as the International Year of Millet, underscoring its importance. This article delves into various methods of production and processing, highlighting opportunities to enhance the production and nutritional qualities of millet. We attribute millets to inadequate rainfall distribution, poor crop management high prices of farm inputs such as fertilizer and pesticides and low adoption of improved varieties by the farmers. It also outlines the constraints, challenges, and future prospects associated with promoting millet as a viable food source for the burgeoning population. Despite the promise that millets hold, they have not received adequate research attention. Therefore, increased research efforts on integrating genomics in genome-wide marker-trait association are imperative, encompassing germplasm collection, protection, evaluation, consumption patterns, development of high-yielding cultivars, processing techniques, and policy interventions. Such initiatives are necessary to bolster the cultivation of millets and harness their potential to address the escalating global food challenge. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) are a comparatively novel class of phytohormones that are involved in the maintenance of plant architecture with key regulation of lateral branching. They are also reported to play an important role in regulating plant responses to various abiotic stresses. The potential of SLs to improve crop resilience and productivity needs to be effectively translated into agriculture. Therefore, both the endogenous biosynthesis of SLs and their exogenous application need to be thoroughly investigated to understand and exploit the mechanism underlying the alleviation of abiotic stress responses. Although several reviews have emphasised the biosynthesis of SLs in plants under abiotic stress, the mechanism underlying the alleviation of stress responses upon exogenous application has been less explored. Accordingly, in this review, although we have briefly discussed the beneficial effects of endogenous production of SLs in different sections, our main focus is to summarise the influence of exogenous SLs on the growth and development of different plant species grown under various abiotic stresses including drought, nutrient, heavy metal, and salinity stress. Apart from providing an overview of the transcriptomic studies conducted to observe the alleviating effects of SLs on abiotic stress responses, the research gaps in this field were briefly discussed. The review provides insight for researchers to conduct further research on SLs and fill the gap so that they can be effectively used for sustainable agriculture. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by elusive underlying mechanisms. Recent attention has focused on the involvement of astrocytes and microglia in ASD pathology. These glial cells play pivotal roles in maintaining neuronal homeostasis, including the regulation of metabolism. Emerging evidence suggests a potential association between ASD and inborn errors of metabolism. Therefore, gaining a comprehensive understanding of the functions of microglia and astrocytes in ASD is crucial for the development of effective therapeutic interventions. This review aims to provide a summary of the metabolism of astrocytes and microglia during post-natal development and the evidence of disrupted metabolic pathways in ASD, with particular emphasis on those potentially important for the regulation of neuronal post-natal maturation by astrocytes and microglia. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs), synthesized in plant roots, play a dual role in modulating plant growth and development, and in inducing the germination of parasitic plant seeds and arbuscular mycorrhizal fungi in the rhizosphere. As phytohormones, SLs are crucial in regulating branching and shaping plant architecture. Despite the significant impact of branching strategies on the yield performance of fruit crops, limited research has been conducted on SLs in these crops. In our study, we identified the transcript sequences of SL biosynthesis and signaling genes in olive (Olea europaea L.) using rapid amplification of cDNA ends. We predicted the corresponding protein sequences, analyzed their characteristics, and conducted molecular docking with bioinformatics tools. Furthermore, we quantified the expression levels of these genes in various tissues using quantitative real‐time PCR. Our findings demonstrate the predominant expression of SL biosynthesis and signaling genes (OeD27, OeMAX3, OeMAX4, OeMAX1, OeD14, and OeMAX2) in roots and lateral buds, highlighting their importance in branching. Treatment with rac‐GR24, an SL analog, enhanced the germination frequency of olive seeds in vitro compared with untreated embryos. Conversely, inhibition of SL biosynthesis with TIS108 increased lateral bud formation in a hard‐to‐root cultivar, underscoring the role of SLs as phytohormones in olives. These results suggest that modifying SL biosynthesis and signaling pathways could offer novel approaches for olive breeding, with potential applicability to other fruit crops. [ABSTRACT FROM AUTHOR]

Background Glucose is an important fuel for the brain. In glucose transporter 1 deficiency syndrome (GLUT1DS), the transport of glucose across the blood–brain barrier is limited. Most individuals with GLUT1DS present with developmental problems, epilepsy, and (paroxysmal) movement disorders, and respond favorably to the ketogenic diet. Similar to ketones, lactate is an alternative energy source for the brain. The aim of this study is to investigate whether intravenous infusion of sodium lactate in children with GLUT1DS has beneficial effects on their epilepsy. Methods We performed a proof of principle study with two subjects with GLUT1DS who were not on a ketogenic diet and suffered from absence epilepsy. After overnight fasting, sodium lactate (600 mmol/L) was infused during 120 minutes, under video electroencephalographic (EEG) recording and monitoring of serum lactate, glucose, electrolytes, and pH. Furthermore, the EEGs were compared with pre-/postprandial EEGs of both subjects, obtained shortly before the study. Results Fasting EEGs of both subjects showed frequent bilateral, frontocentral polyspike and wave complexes. In one subject, no more epileptic discharges were seen postprandially and after the start of lactate infusion. The EEG of the other subject did not change, neither postprandially nor after lactate infusion. Serum pH, lactate, and sodium changed temporarily during the study. Conclusion This study suggests that sodium lactate infusion is possible in individuals with GLUT1DS, and may have potential therapeutic effects. Cellular abnormalities, beyond neuronal energy failure, may contribute to the underlying disease mechanisms of GLUT1DS, explaining why not all individuals respond to the supplementation of alternative energy sources. [ABSTRACT FROM AUTHOR]

Cereal grains have been domesticated largely from food grains to feed and malting grains. Barley (Hordeum vulgare L.) remains unparalleled in its success as a primary brewing grain. However, there is renewed interest in "alternative" grains for brewing (and distilling) due to attention being placed on flavor, quality, and health (i.e., gluten issues) aspects that they may offer. This review covers basic and general information on "alternative grains" for malting and brewing, as well as an in-depth look at several major biochemical aspects of these grains including starch, protein, polyphenols, and lipids. These traits are described in terms of their effects on processing and flavor, as well as the prospects for improvement through breeding. These aspects have been studied extensively in barley, but little is known about the functional properties in other crops for malting and brewing. In addition, the complex nature of malting and brewing produces a large number of brewing targets but requires extensive processing, laboratory analysis, and accompanying sensory analysis. However, if a better understanding of the potential of alternative crops that can be used in malting and brewing is needed, then significantly more research is required. [ABSTRACT FROM AUTHOR]

Introduction: An active metabolite of buprenorphine (BUP), called norbuprenorphine (NorBUP), is implicated in neonatal opioid withdrawal syndrome when BUP is taken during pregnancy. Therefore, reducing or eliminating metabolism of BUP to NorBUP is a novel strategy that will likely lower total fetal exposure to opioids and thus improve offspring outcomes. Precision deuteration alters pharmacokinetics of drugs without altering pharmacodynamics. Here, we report the synthesis and testing of deuterated buprenorphine (BUP-D2). Methods: We determined opioid receptor affinities of BUP-D2 relative to BUP with radioligand competition receptor binding assays, and the potency and efficacy of BUP-D2 relative to BUP to activate G-proteins via opioid receptors with [35S]GTP-S binding assays in homogenates containing the human mu, delta, or kappa opioid receptors. The antinociceptive effects of BUP-D2 and BUP were compared using the warm-water tail withdrawal assay in rats. Blood concentration versus time profiles of BUP, BUP-D2, and NorBUP were measured in rats following intravenous BUP-D2 or BUP injection. Results: The synthesis provided a 48% yield and the product was =99% deuterated. Like BUP, BUP-D2 had sub-nanomolar affinity for opioid receptors. BUP-D2 alsoactivated opioid receptors and induced antinociception with equal potency and efficacy as BUP. The maximum concentration and the area under the curve of NorBUP in the blood of rats that received BUP-D2 were over 19- and 10-fold lower, respectively, than in rats that received BUP. Discussion: These results indicate that BUP-D2 retains key pharmacodynamic properties of BUP and resists metabolism to NorBUP and therefore holds promise as an alternative to BUP. [ABSTRACT FROM AUTHOR]

Introduction: Sorghum is a resilient and widely cultivated grain crop used for feed and food. However, it's grain is deficient in lysine, an essential amino acid. This is due to the primary seed storage proteins, the alpha-kafirins, lacking lysine. It has been observed that reductions in alpha-kafirin protein results in rebalancing of the seed proteome and a corresponding increase in non-kafirin proteins which leads to an increased lysine content. However, the mechanisms underlying proteome rebalancing are unclear. This study characterizes a previously developed gene edited sorghum line, with deletions at the alpha kafirin locus. Methods: A single consensus guide RNA leads to tandem deletion of multiple members of the gene family in addition to the small target site mutations in remaining genes. RNA-seq and ATAC-seq were utilized to identify changes in gene expression and chromatin accessibility in developing kernels in the absence of most alpha-kafirin expression. Results: Several differentially accessible chromatin regions and differentially expressed genes were identified. Additionally, several genes upregulated in the edited sorghum line were common with their syntenic orthologues differentially expressed in maize prolamin mutants. ATAC-seq showed enrichment of the binding motif for ZmOPAQUE 11, perhaps indicating the transcription factor's involvement in the kernel response to reduced prolamins. Discussion: Overall, this study provides a resource of genes and chromosomal regions which may be involved in sorghum's response to reduced seed storage proteins and the process of proteome rebalancing. [ABSTRACT FROM AUTHOR]

Strigolactones regulate shoot branching and many aspects of plant growth, development, and allelopathy. Strigolactones are often discussed alongside auxin because they work together to inhibit shoot branching. However, the roles and mechanisms of strigolactones and how they act independently of auxin are still elusive. Additionally, there is still much in general to be discovered about the network of molecular regulators and their interactions in response to strigolactones. Here, we conducted an experiment in Arabidopsis with physiological treatments and strigolactone mutants to determine transcriptional pathways associated with strigolactones. The three physiological treatments included shoot tip removal with and without auxin treatment and treatment of intact plants with the auxin transport inhibitor, N‐1‐naphthylphthalamic acid (NPA). We identified the glucosinolate biosynthesis pathway as being upregulated across strigolactone mutants indicating strigolactone–glucosinolate crosstalk. Additionally, strigolactone application cannot restore the highly branched phenotype observed in glucosinolate biosynthesis mutants, placing glucosinolate biosynthesis downstream of strigolactone biosynthesis. Oxidative stress genes were enriched across the experiment suggesting that this process is mediated through multiple hormones. Here, we also provide evidence supporting non‐auxin‐mediated, negative feedback on strigolactone biosynthesis. Increases in strigolactone biosynthesis gene expression seen in strigolactone mutants could not be fully restored by auxin. By contrast, auxin could fully restore auxin‐responsive gene expression increases, but not sugar signaling‐related gene expression. Our data also point to alternative roles of the strigolactone biosynthesis genes and potential new signaling functions of strigolactone precursors. In this study, we identify a strigolactone‐specific regulation of glucosinolate biosynthesis genes indicating that the two are linked and may work together in regulating stress and shoot branching responses in Arabidopsis. Additionally, we provide evidence for non‐auxin‐mediated feedback on strigolactone biosynthesis and discuss this in the context of sugar signaling. [ABSTRACT FROM AUTHOR]

Aging is an inevitable process that all individuals experience, of which the extent differs among individuals. It has been recognized as the risk factor of neurodegenerative diseases by affecting gut microbiota compositions, microglia, and cognition abilities. Aging‐induced changes in gut microbiota compositions have a critical role in orchestrating the morphology and functions of microglia through the gut‐brain axis. Gut microbiota communicates with microglia by its secreted metabolites and neurotransmitters. This is highly associated with age‐related cognitive declines. Here, we review the main composition of microbiota in the aged individuals, outline the changes of the brain in age‐related cognitive decline from a neuroinflammation perspective, especially the changes of morphology and functions of microglia, discuss the crosstalk between microbiota and microglia in the aged brain and further highlight the role of microbiota‐microglia connections in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease). [ABSTRACT FROM AUTHOR]

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Central nervous system (CNS) is always an area of thrust where continuous efforts are required to achieve targeted drug delivery. The blood brain barrier (BBB) is the chief interfering element in the development of effective neurotherapeutics and efficient drug delivery to the CNS. Large neutral amino acid (LAT1) is the one which is the most promising gateway and belongs to the carrier-mediated transporters (CMTs), which is also called as Solute Carrier Family 7 Member 5 (SLC7A5). LAT1 is a sodium- and pH-independent transporter, which not only supplies essential amino acids to cells but also plays an important role in the facilitated transport of thyroid hormones, pharmaceuticals and metabolites into the brain by breaching the BBB. Levodopa, melphalan, gabapentin, brexpiprazole, valbenazine and a-methyldopa are already known drugs which cross the BBB via LAT1 mediated transport; therefore, the LAT1 is thought to be a potential target for piercing the BBB. This review is a combined effort to shed light on the pharmaceutical importance of this transporter and how this can be exploited further as a mediator for drugs to cross the BBB. [ABSTRACT FROM AUTHOR]

We verified if cocaine-induced peripheral activation might disrupt [ 18 F]FDG brain uptake after a cocaine challenge and suggested an optimal protocol to measure cocaine-induced brain metabolic alterations in mice. C57Bl/6 male mice were injected with [ 18 F]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [ 18 F]FDG administration and after 5 min received saline or cocaine (20 mg/kg). The animals in group 1 (n = 5) were then evaluated in the open field for 30 min and those from group 2 (n = 6) were kept alone in a home cage for the same period. Forty-five minutes after [ 18 F]FDG administration, images were acquired for 30 min. Group 3 (n = 6) was kept anesthetized and image acquisition started immediately after tracer injection, for 75 min. Saline (Day 1) or cocaine (Day 2) was injected 5 min after starting acquisition. Another set of animals (n = 5) were treated with cocaine every other day for 10 days or saline (n = 6) and were scanned with the dynamic protocol to verify its efficacy. [ 18 F]FDG uptake increased after cocaine administration when compared to baseline only in animals kept under anesthesia. No brain effect of cocaine was observed in animals submitted to the open field or kept in the home cage. The use of anesthesia is essential to visualize cocaine-induced changes in brain metabolism by [ 18 F]FDG PET, providing an interesting preclinical approach to investigate naïve subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder., (© 2022 Wiley Periodicals LLC.)