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This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste-malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste-malaise convergence during CTA acquisition depending on the strength of the aversion. Keywords: acquisition, amygdala, accumbens, insular cortex, learning

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Consumption of caffeine, a non-selective adenosine A2Areceptor (A2AR) antagonist, reduces the risk of developing Alzheimer’s disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2Areceptors as important molecular targets to consider against AD and Tauopathies.

A single injection of 10(5) U/kg of recombinant rat IFN-gamma increases the amount of tissue dendritic cells up to sixfold, and concomitantly induces the (capillary) endothelial cells to express class II MHC antigens. Both responses peak on the third day after IFN-gamma injection, and the antigen expression returns to basic levels on day 7. Simultaneous administration of 1 mg/kg/d of methylprednisolone entirely abolishes both responses. These observations demonstrate, for the first time, that IFN-gamma and steroids have antagonistic effects on class II MHC antigen presentation in tissue, and suggest that one immunosuppressive mechanism of glucocorticosteroids in organ transplantation is downregulation of graft antigenicity.

The aim of this work is to determine the effect of low frequency current (L) versus medium frequency current (M) in order to generate a different force level on soleus and gastrocnemius muscles.The experiment was conducted on 10 healthy, male volunteer subjects aged from 19 to 21 who provided informed consent to participate in the experiment. None of the subjects had experienced electrostimulation (ES) procedures before. The subjects were seated with vertical legs and horizontal thighs. Isometric force of the gastrocnemius and soleus muscles was measured using a strain gage dynamometer (100 daN). The transducer was adjusted on the knee, along the vertical axis of the leg.For the conditions of ES, a bi-phasic, symmetrical square wave signal was applied at each of five low frequencies: 20, 40, 60, 80 and 100 Hz and at each of six medium frequencies (2222 Hz) modulated or not, to yield 20, 40, 60, 80, 100 bursts of pulses. Maximum voluntary contraction (MVC) was also recorded. The phase duration was constant throughout 180 μs. The current level was set individually for each subject at the maximum that could be tolerated and applied during 10 s. Each contractile condition was randomly chosen.The forces produced by the different regimen of ES used are significantly different (P < 0.001). For each type of stimulation we got tetanic contractions. After an initial ramp, a nearly flat curve corresponding to tetanus was reached.For a 60 hz low frequency current, the force production reached 16% of MVC for a mean intensity of 58 mA, corresponding to a charge of 1253 μC. For medium frequency with a 80 Hz modulation, the maximum force values (64% of MVC) were reached after 3 s stimulation. The mean intensity used was 62 mA with a charge nearly 23000 μC.In order to produce a maximal muscular tension, low frequencies (about 60 hz) seem more suitable. For infra maximal contraction medium modulation frequencies can be used.

The distribution and succession of epiphytic and other associated lichens on blackthorn (Prunus spinosa) growing on the shingle at Dungeness is described. Some 33 epiphytic species, which exhibited a range of ecological strategies from pioneer to late colonizers, were recorded. Both the rate of change of status (age) of blackthorns and the progress of lichen colonization seemed to depend on whether the bushes were growing directly on shingle or on adjacent alluvial soil; both processes seeming to be more rapid on the former substratum. Terricolous lichens, of which 18 were recorded, generally appeared late in the succession and mostly amongst bushes growing on shingle. Rabbits often invaded the blackthorns, especially those on alluvium, and probably contributed to the lack of terrestrial lichens under these bushes. Blackthorns growing on shingle tended to be more prostrate in form than those on alluvium. 1996 The British Lichen Society

The present study aimed at documenting the neurobiological substrate of taste-potentiated odor aversion (TPOA) in the rat. The role of several temporal lobe structures in discriminative TPOA learning was questioned. The effects of excitotoxic lesions (ibotenate) of the basolateral amygdaloid nucleus, the central amygdaloid nucleus, the caudate putamen nucleus, and aspirative lesion of the entorhinal cortex were studied. The results show that only basolateral amygdaloid nucleus (ABL) damage impaired TPOA. This effect was selective of TPOA, since it spared conditioned taste aversion (CTA) and olfactory perception. in order to find out which process in TPOA requires normal functioning of the ABL, the effects of microinjections of a GABA_A agonist (muscimol) into the ABL at various stages of the experiment were examined. The results show that application of muscimol during the acquisition, before or after the presentation of the odor-taste stimulus, impaired TPOA without affecting CTA. Contrastingly, application of muscimol before the test impaired neither TPOA nor CTA. These results suggest that ABL is involved in the acquisition but not in the retrieval of TPOA. The efficacy of muscimol microinjected after the presentation of the odor-taste stimulus further suggests that the deficit is not due to a sensory impairment but rather to the disruption of a memory process, critical for TPOA.Copyright 1995, 1999 Academic Press,Inc.

Cellular DNA content of primary tumours from 280 patients with operable breast cancer was determined by flow cytometry using nuclei from paraffin sections stained with DAPI, and 199 of these patients were followed for 8-13 years after surgery. Tumours from 67 patients have also been analyzed for their DNA content using single cell suspensions from fresh tumour tissue stained with mithramycin and ethidium bromide, and the results compared with those obtained from paraffin blocks of the same tumours. Overall 60% of the tumours contained cells with abnormal DNA content (DNA-aneuploid populations). Survival and disease free interval were not significantly different in patients with DNA-diploid and DNA-aneuploid tumours when analysed by Mantel's life table method. There was however, an early advantage for patients with DNA-diploid tumours: during the first 30 months after surgery DNA-aneuploidy was associated with higher rate of recurrence and shorter survival. DNA-aneuploidy was strongly related to histological grade. Thus 11/49 (22%) grade I, 60/102 (59%) grade II, and 96/129 (74%) grade III tumours were DNA-aneuploid. Although there was no significant difference in survival of patients with DNA-diploid and DNA-aneuploid tumours overall, there appears to be an unexpected association between DNA-aneuploidy and better survival in grade II patients (P less than 0.01); a similar trend was observed for grade I patients. Although the proportion of DNA-aneuploid tumours was similar in oestrogen receptor positive and negative tumours, DNA-aneuploidy was associated with lower levels of oestrogen receptors in comparison to DNA-diploid tumours. Comparison between the modal DNA values of fresh and paraffin embedded samples showed high rate of comparability (64/67, P less than 0.0001).

Correction to: Molecular Psychiatry advance online publication, 2 December 2014; doi:10.1038/mp.2014.151 Following publication of this paper, the authors noticed that the eighth author’s name was misspelled. The author’s name should have been listed as E Marciniak.