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Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy. Synopsis: This study highlights the importance of metabolic symbiosis dependent on lactate and lactate dehydrogenase isoforms (LDHA and B) in glioblastoma development. Inhibiting both lactate dehydrogenases may be a novel potential therapeutic approach for targeting glioblastoma. Lactate, which is produced in hypoxic environments, is secreted and taken up by oxidative cells to fuel the Krebs cycle to promote growth and invasion.Only double knockout of LDHA/B abolished lactate production, reduced tumor growth and invasion, and prolonged mouse survival.Tumors that no longer express LDH become more oxidative and more sensitive to radiation.The use of the LDH inhibitor stiripentol in clinical practice may be therapeutically relevant for glioblastoma. [ABSTRACT FROM AUTHOR]

Recreational fishing is increasingly recognised as an important source of mortality for marine fish populations. In the United States, estimates of marine recreational catch and effort were recently revised for the time period 1981 and beyond, and for many species, the revised estimates were substantially higher than the original values. Here, the proportion of total landings that came from the recreational sector in the Southeast US Atlantic was quantified. The proportions for 22 oceanic species and for all species combined were computed, using a full time series of landings (1981–2016) and a more recent time series (1999–2016). For the full and recent time series, landings of most species (15/22 and 17/22, respectively) were dominated by the recreational sector. For all species combined, 71% of landings in the full time series were from the recreational sector, and 76% in the recent time series. Trend analysis indicated that most species had a stable or increasing proportion of landings from the recreational sector. In addition, stock assessments were conducted on four species, and the catch revisions increased the estimated scale of abundance and, in some cases, affected stock or fishery status. This work underscores the importance of recreational fishing for marine resource management. [ABSTRACT FROM AUTHOR]

In epilepsy, the GABA and glutamate balance may be disrupted and a transient decrease in extracellular calcium occurs before and during a seizure. Flow Cytometry based fluorescence activated particle sorting experiments quantified synaptosomes from human neocortical tissue, from both epileptic and non-epileptic patients (27.7% vs. 36.9% GABAergic synaptosomes, respectively). Transporter-mediated release of GABA in human and rat neocortical synaptosomes was measured using the superfusion technique for the measurement of endogenous GABA. GABA release was evoked by either a sodium channel activator or a sodium/potassium-ATPase inhibitor when exocytosis was possible or prevented, and when the sodium/calcium exchanger was active or inhibited. The transporter-mediated release of GABA is because of elevated intracellular sodium. A reduction in the extracellular calcium increased this release (in both non-epileptic and epileptic, except Rasmussen encephalitis, synaptosomes). The inverse was seen during calcium doubling. In humans, GABA release was not affected by exocytosis inhibition, that is, it was solely transporter-mediated. However, in rat synaptosomes, an increase in GABA release at zero calcium was only exhibited when the exocytosis was prevented. The absence of calcium amplified the sodium/calcium exchanger activity, leading to elevated intracellular sodium, which, together with the stimulation-evoked intracellular sodium increment, enhanced GABA transporter reversal. Sodium/calcium exchange inhibitors diminished GABA release. Thus, an important seizure-induced extracellular calcium reduction might trigger a transporter- and sodium/calcium exchanger-related anti-seizure mechanism by augmenting transporter-mediated GABA release, a mechanism absent in rats. Uniquely, the additional increase in GABA release because of calcium-withdrawal dwindled during the course of illness in Rasmussen encephalitis. [ABSTRACT FROM AUTHOR]