Brain-borne IL-1 adjusts glucoregulation and provides fuel support to astrocytes and neurons in an autocrine/paracrine manner.

It is still controversial which mediators regulate energy provision to activated neural cells, as insulin does in peripheral tissues. Interleukin-1β (IL-1β) may mediate this effect as it can affect glucoregulation, it is overexpressed in the 'healthy' brain during increased neuronal activity, and it supports high-energy demanding processes such as long-term potentiation, memory and learning. Furthermore, the absence of sustained neuroendocrine and behavioral counterregulation suggests that brain glucose-sensing neurons do not perceive IL-1β-induced hypoglycemia. Here, we show that IL-1β adjusts glucoregulation by inducing its own production in the brain, and that IL-1β-induced hypoglycemia is myeloid differentiation primary response 88 protein (MyD88)-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. Furthermore, we found that, opposite to insulin, IL-1β stimulates brain metabolism. This effect is absent in MyD88-deficient mice, which have neurobehavioral alterations associated to disorders in glucose homeostasis, as during several psychiatric diseases. IL-1β effects on brain metabolism are most likely maintained by IL-1β auto-induction and may reflect a compensatory increase in fuel supply to neural cells. We explore this possibility by directly blocking IL-1 receptors in neural cells. The results showed that, in an activity-dependent and paracrine/autocrine manner, endogenous IL-1 produced by neurons and astrocytes facilitates glucose uptake by these cells. This effect is exacerbated following glutamatergic stimulation and can be passively transferred between cell types. We conclude that the capacity of IL-1β to provide fuel to neural cells underlies its physiological effects on glucoregulation, synaptic plasticity, learning and memory. However, deregulation of IL-1β production could contribute to the alterations in brain glucose metabolism that are detected in several neurologic and psychiatric diseases.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.174.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

OBJECTIVE Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. DESIGN Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. RESULTS Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). CONCLUSION A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD.

Molecular mechanism of jet fuel induced immune suppression

Dermal exposure to jet fuel suppresses the immune response. Immune regulatory cytokines, and biological modifiers, including platelet activating factor, prostaglandin E2, and interleukin-10 have all been implicated in the pathway leading to immunosuppression. It is estimated that approximately 260 different hydrocarbons are found in JP-8 (jet propulsion-8) jet fuel, and the identity of the immunotoxic compound is not known. The recent availability of synthetic jet fuel (S-8), which is devoid of aromatic hydrocarbons, made it feasible to design experiments to test the hypothesis that the aromatic hydrocarbons are responsible for jet fuel induced immune suppression. Applying S-8 to the skin of mice does not up-regulate the expression of epidermal cyclooxygenase-2 nor does it induce immune suppression. Adding back a cocktail of 7 of the most prevalent aromatic hydrocarbons found in jet fuel to S-8 up-regulated cyclooxygenase-2 expression and induced immune suppression. Cyclooxygenase-2 induction can be initiated by reactive oxygen species (ROS). JP-8 treated keratinocytes increased ROS production, S-8 did not. Antioxidant pre-treatment blocked jet fuel induced immune suppression and cyclooxygenase-2 up-regulation. Accumulation of reactive oxygen species induces oxidant stress and affects activity of ROS sensitive transcription factors. JP-8 induced activation of NFκB while S-8 did not. Pre-treatment with antioxidants blocked activation of NFκB and parthenolide, an NFκB inhibitor, blocked jet fuel induced immune suppression and cyclooxygenase-2 expression in skin of treated mice. p65 siRNA transfected keratinocytes demonstrated NFκB is critically involved in jet fuel induced COX-2 expression. These findings clearly implicate the aromatic hydrocarbons found in jet fuel as the agents responsible for inducing immune suppression, in part by the production of reaction oxygen species, NFκB dependent up-regulation of cyclooxygenase-2, and the production of immune regulatory factors and cytokines. ^

(Table 1) Vesicularity of basalts recovered at DSDP Holes 49-407, 49-408, and 49-409

Average vesicularity of basalt drilled at three sites on the west flank of the Reykjanes Ridge increases with decreasing age. This change apparently records concomitant decrease in water depth at the ridge crest where the basalt was erupted and suggests substantial upward growth of the crest during the past 35 Myr.

Manganese nodules recovered by R/V Vityaz expedition

Uranium, radium, thorium and ionium were determined directly on seven concretions from three stations in the Indian Ocean, and on two concretions and a manganese-rich crust from two stations in the Pacific Ocean. The uranium content averages 3 to 5 gamma/g and the thorium content varies only slightly, but the Th/U ratio in the concretions is typically 2 to 5 in the Indian Ocean and 5 to 15.5 in the Pacific. The ionium content ranges from 1.0 x 10-9 to 3.6 10**-9 g/g in concretions from both oceans. Radium is more abundant in specimens from the Pacific Ocean (Ra = 3 - 12.7 x 10**-11 g/g) than from the Indian Ocean (1.5 - 5.2 x 10**-11 g/g). Analyses for Ca, Mn, Fe, Si, Ni, P, and ignition loss are also given. Radioactive equilibria between uranium, ionium, and radium are strongly disturbed throughout the concretions, and the RA/U and lo/U ratios generally exceed equilibrium ratios. Migration of radium from interior layers was established, so that neither determination of the ages of the concretions nor of their rates of growth can be considered reliable. The age of the concretions cannot exceed 800,000 years, and all grew within relatively short periods of time; there may have been "dormant" periods during growth. Estimates of growth rates are calculated from the radium and ionium contents; they show marked discordance.

(Figure 2) Range and distribution chart of dinoflagellate cysts recovered from Campanian to Maestrichtian sediments at DSDP Hole 95-612

Fifty-nine samples from the basal 110 m of DSDP Hole 612 (United States Atlantic Margin) were analyzed for palynomorph content. In total, 84 species and subspecies of dinoflagellate cysts were recorded which, on comparison with published data and shipboard analyses, indicate a Campanian to Maestrichtian age for this part of the succession. The Campanian/Maestrichtian contact is taken to occur in the upper part of Core 612-69.

Table I: Schedule of the drilling operation and lengths of the recovered core material for the boreholes on Vernagtferner in 1979

In 1979 a core drilling project was carried out on Vernagtferner in the Oetztal Alps (Austria). This report describes the field work of the drilling project, the recovered core material and the occurrence of water in the boreholes and compiles the succeding investigation program.

Mass-accumulation rates for the non-authigenic, inorganic, crystalline, eolian component of sediments recovered at DSDP Sites 62-464 to 62-466

The mass-accumulation rate (MAR) of the non-authigenic, inorganic, crystalline component of deep-sea sediments from the Pacific aseismic rises apparently reflects influx of eolian sediment. The eolian sediment usually is dominated by volcanic material, except during glacial times. Sediments from Hess Rise provide a discontinuous record of eolian MARs. During Albian to Cenomanian time, the influx of volcanic material was fairly high (0.35-0.6 g/cm**2/10**3 yr), recording the latest stages of the Albian volcanism that formed Hess Rise. From the Campanian through the Paleocene, influx of eolian sediment was low, averaging 0.03 g/cm**2/10**3 yr. None of the four Hess Rise drill sites show evidence of the Late Cretaceous volcanic episode recorded at many sites now in the equatorial to subtropical Pacific. Pliocene to Pleistocene samples record a peak in volcanic influx about 4 to 5 m.y. ago, which has been well documented elsewhere. The several-fold increase in eolian accumulation rates elsewhere which are correlated with the onset of severe northernhemisphere glaciation 2.5 m.y. ago is not obvious in the Hess Rise data.