VTA and the Papez circuit (hypothalamus-mammillary bodies, mamillo-thalamic tract, anterior thalamic nuclei, cingulate cortex and hippo/parahippocampus), implicated in reward-motivated learning and memory processing, 4 appeared to be involved in these processes. Activation in the septal region in placebo nonresponders recalling was also observed. If confirmed, this effect would be consistent with the memory impairment observed after intraseptal m-opioid agonist administration, 9 through inhibition of the septohippocampal GABAergic neurons. 10 This report extends previous findings on the role of the m-opioid neurotransmitter system in acute placebo responses, 2 and highlights a novel role of this system in the formation of memories of placebo analgesic effects in distinct neural circuits. These processes provide a framework to understand stimulus learning and therapeutic effect associations, of importance for the sustainability of placebo effects.
Rat intestinal microvillous alkaline phosphatases are secreted bidirectionally from the enterocyte attached to a phospholipid-rich membrane (surfactant-like particle). To determine the intracellular pathways for newly synthesized alkaline phosphatases and for the extracellular enzyme-particle complex in the intestinal mucosa, pulse-chase experiments were performed. Synthesis of both isoforms of alkaline phosphatase in fasted rats peaked in the Golgi at 15-30 min and in the microvillous membrane at 60 min, without intermediate localization in the basolateral membranes. A second peak of incorporation was found at 15-30 min in scrapings obtained from the apical surface of the enterocytes. These results demonstrate a dominant direct Golgi-to-microvillous membrane transport for newly synthesized alkaline phosphatase. An additional precursor pool(s) appears responsible for the early appearance of enzyme in the lumen. Newly synthesized alkaline phosphatase isoforms and the 97-kDa protein of surfactant-like particles showed parallel patterns of appearance in enterocytes, luminal washings, and lamina propria after triacylglycerol feeding and were preferentially secreted into the lumen and lamina propria at times (5-7 h) when enterocyte content of these newly synthesized proteins had declined toward basal rates. Enhanced secretion of newly synthesized proteins for hours after fat feeding could explain the prolonged rise in serum and luminal washings of both the enzyme and the particle.
Abstract. The use of co-located multiple spectroscopic techniques can provide detailed information on the atmospheric processes regulating aerosol chemical composition and mixing state. So far, field campaigns heavily equipped with aerosol mass spectrometers have been carried out mainly in large conurbations and in areas directly affected by their outflow, whereas lesser efforts have been dedicated to continental areas characterised by a less dense urbanisation. We present here the results obtained at a background site in the Po Valley, Italy, in summer 2009. For the first time in Europe, six state-of-the-art spectrometric techniques were used in parallel: aerosol time-of-flight mass spectrometer (ATOFMS), two aerosol mass spectrometers (high-resolution time-of-flight aerosol mass spectrometer – HR-ToF-AMS and soot particle aerosol mass spectrometer – SP-AMS), thermal desorption aerosol gas chromatography (TAG), chemical ionisation mass spectrometry (CIMS) and (offline) proton nuclear magnetic resonance (1H-NMR) spectroscopy. The results indicate that, under high-pressure conditions, atmospheric stratification at night and early morning hours led to the accumulation of aerosols produced by anthropogenic sources distributed over the Po Valley plain. Such aerosols include primary components such as black carbon (BC), secondary semivolatile compounds such as ammonium nitrate and amines and a class of monocarboxylic acids which correspond to the AMS cooking organic aerosol (COA) already identified in urban areas. In daytime, the entrainment of aged air masses in the mixing layer is responsible for the accumulation of low-volatility oxygenated organic aerosol (LV-OOA) and also for the recycling of non-volatile primary species such as black carbon. According to organic aerosol source apportionment, anthropogenic aerosols accumulating in the lower layers overnight accounted for 38% of organic aerosol mass on average, another 21% was accounted for by aerosols recirculated in residual layers but still originating in northern Italy, while a substantial fraction (41%) was due to the most aged aerosols imported from transalpine areas. The different meteorological regimes also affected the BC mixing state: in periods of enhanced stagnation and recirculation of pollutants, the number fraction of the BC-containing particles determined by ATOFMS was 75% of the total, while in the days of enhanced ventilation of the planetary boundary layer (PBL), such fraction was significantly lower (50%) because of the relative greater influence of non-BC-containing aerosol local sources in the Po Valley. Overall, a full internal mixing between BC and the non-refractory aerosol chemical components was not observed during the experiment in this environment.
Tuberous sclerosis complex (TSC) is a common genetic disorder in which affected individuals can develop mental retardation, developmental brain defects, and seizures. Two genetic loci are responsible for TSC: TSC1 on chromosome 9q and TSC2 on chromosome 16p. Here, we report our analysis of TSC1 (hamartin) and TSC2 (tuberin) protein expression in the central nervous system (CNS). Both tuberin and hamartin are expressed in neurons and astrocytes where they physically interact. In the mouse cerebellum in vivo, tuberin predominantly localizes to the perinuclear region of the Purkinje cell, whereas hamartin is distributed along neuronal or astrocytic processes. In contrast, both hamartin and tuberin demonstrate similar neuronal expression patterns in pure neuronal cultures in vitro. Additionally, hamartin is highly expressed in astrocytes in mixed neuron-glia cultures in vitro, suggesting that hamartin may be important for astrocyte growth control. Unlike tuberin, loss of hamartin expression was not observed in sporadic astrocytomas. These results suggest that tuberin and hamartin may differentially contribute to the CNS pathology in TSC.
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