Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal (P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise ( approximately 60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion.     

Human pluripotent stem cells identify molecular targets of trisomy 12 in chronic lymphocytic leukemia patients

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Intraguild interactions between two egg parasitoids exploring host patches

Intraguild interactions between two egg parasitoids, Trissolcus basalis (Hymenoptera: Scelionidae) and Ooencyrtus telenomicida (Hymenoptera: Encyrtidae), exploring egg masses of the Southern Green Stink Bug (SGSB) Nezara viridula (Heteroptera: Pentatomidae), were investigated in laboratory conditions by single, simultaneous and sequential host attack experiments. Mortality of N. viridula eggs was higher in simultaneous and sequential releases compared to single species releases. In simultaneous host exploitations, T. basalis females displayed an aggressive behavior against O. telenomicida females. The outcome of multiparasitism showed that interspecific larval competition was dominated by O. telenomicida regardless of the sequence in which oviposition occurred and which parasitoid was or was not simultaneously released in the patch. Finally, O. telenomicida can successfully develop in hosts already parasitized by T. basalis up to seven days earlier, acting as a facultative hyperparasitoid, so that intraguild predation (IGP) also occurred. The ecological factors that allow species coexistence and the role played by competition in biological control programs are discussed.     

Floral abnormalities in field grown “Tigrina” plants from xHaynaldoticum sardoum Meletti et Onnis (Gramineae)

A ‘tigrina’ mutant stock of xHaynaldoticum sardoum Meletti et Onnis grown under field conditions produced high frequency spikes with abnormal stamens and pistils. The abnormalities occurred mostly in the stamens, which frequently changed to either pseudoovaries, or leaf-shaped structures or, in extreme cases, did not form at all. The developmental abnormalities of the stamens resulted in male sterility in the whole or in part of the spike. It is proposed that the “tigrina” status changes the physiology of the plant (e.g. photosynthetic activity) in such a way that it responds with floral abnormalities brought about by environmental conditions which permit normal flower development in control (non-mutant) plants.     

High Sensitivity of Glutamate Uptake to Extracellular Free Arachidonic Acid Levels in Rat Cortical Synaptosomes and Astrocytes

By using both synaptosomes and cultured astrocytes from rat cerebral cortex, we have investigated the inhibitory action of arachidonic acid on the high-affinity glutamate uptake systems, focusing on the possible physiological significance of this mechanism. Application of arachidonic acid (1-100 microM) to either preparation leads to fast (within 30 s) and largely reversible reduction in the uptake rate. When either melittin (0.2-1 microgram/ml), a phospholipase A2 activator, or thimerosal (50-200 microM), which inhibits fatty acid reacylation in phospholipids, is applied to astrocytes, both an enhancement in extracellular free arachidonate and a reduction in glutamate uptake are seen. The two effects display similar dose dependency and time course. In particular, 10% uptake inhibition correlates with 30% elevation in free arachidonate, whereas inhibition greater than or equal to 60% is paralleled by threefold stimulation of arachidonate release. In the presence of albumin (1-10 mg/ml), a free fatty acid-binding protein, inhibition by either melittin, thimerosal, or arachidonic acid is prevented and an enhancement of glutamate uptake above the control levels is observed. Our data show that neuronal and glial glutamate transport systems are highly sensitive to changes in extracellular free arachidonate levels and suggest that uptake inhibition may be a relevant mechanism in the action of arachidonic acid at glutamatergic synapses.     

A computer model of intermediate cerebellum dynamic operations in motor control

An intermediate cerebellum theoretical model for processing central programming discharges and muscle force signals is described which can perform a correct motor task under different peripheral perturbations (loads). An indispensable condition is that the simulated interpositus nucleus cells controlling a given effector (muscle) are inhibited by impulses coming from that effector (negative feedback from muscle force detectors). The hypothesis is proposed that the intermediate cerebellum can act via the rubrospinal tract as an interface between programming and executing motor structures.     

β-Arrestin 2-mediated heterologous desensitization of IGF-IR by prolonged exposure of SH-SY5Y neuroblastoma cells to a mu opioid agonist

Prolonged (12 h) exposure of SH-SY5Y neuroblastoma cells to the mu-opioid receptor (MOPr) agonist [D-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (DAMGO) causes homologous desensitization as well as heterologous desensitization of the extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation induced by insulin-like growth factor (IGF)-I. Brief (15 min) but not prolonged exposure to DAMGO transregulates the insulin-like growth factor-I (IGF-I) receptor, as evidenced by its phosphorylation in the absence of IGF-I. Silencing of β-arrestin 2 uncouples the crosstalk between the two receptors, thus maintaining IGF-I-mediated receptor phosphorylation and ERK 1/2 activation even after prolonged DAMGO exposure. Furthermore, MOPr-induced activation of IGF-I receptor requires the tyrosine kinase c-Src.