Lesions of retrosplenial cortex spare immediate-early gene activity in related limbic regions in the rat

The retrosplenial cortex forms part of a network of cortical and subcortical structures that have particular importance for spatial learning and navigation in rodents. This study examined how retrosplenial lesions affect activity in this network by visualising the expression of the immediate-early genes c-fos and zif268 after exposure to a novel location. Groups of rats with extensive cytotoxic lesions (areas 29 and 30) and rats with lesions largely confined to area 30 (dysgranular cortex) were compared with their respective control animals for levels of c-fos expression measured by immunohistochemistry. These cortical lesions had very limited effects on distal c-fos activity. Evidence of a restricted reduction in c-fos activity was seen in the septal dentate gyrus (superior blade) but not in other hippocampal and parahippocampal subareas, nor in the anterior cingulate and prelimbic cortices. Related studies examined zif268 activity in those cases with combined area 29 and 30 lesions. The only clear evidence for reduced zif268 activity following retrosplenial cell loss came from the septal CA3 area. The confined impact of retrosplenial tissue loss is notable as, by the same immediate-early gene measures, retrosplenial cortex is itself highly sensitive to damage in related limbic areas, showing a marked c-fos and zif268 hypoactivity across all of its subareas. This asymmetry in covert pathology may help to explain the apparent disparity between the severity of learning deficits after retrosplenial cortex lesions and after lesions in either the hippocampus or the anterior thalamic nuclei

Effect of post-harvest anti-sprouting treatment with spearmint essential oil on acrylamide formation in potato crisps

The control of sprouts is essential to ensure quality of stored potatoes destined for the processing market. This paper investigates the effects of post-harvest treatment of tubers with spearmint essential oil (MEO) as sprouts suppressant, on both precursors of and acrylamide formation in potato crisps. Two trials were designed using two varieties of potato cultivars, to investigate the effect of a single MEO application over time and of one and two MEO applications compared to controls. A lower amount of reducing sugars was found in treated potatoes from both varieties after one day from treatment (Lady Claire: −26.8%; Taurus: −59.5%), which for Taurus tubers corresponded to lower acrylamide content in the crisps (−72.8%). Lower acrylamide levels were quantified in Lady Claire treated twice with MEO (−70.2%) and in controls (−59.6%) compared with potatoes treated once. Both trials demonstrate that treatment with MEO has no overall negative impact on acrylamide formation. Furthermore, no substantial change can be observed in the amino acidic and sugar profile of the tubers, which cannot be attributed to variability among tubers. These findings support the effective and safe use of MEO to control sprouting of potatoes destined to the processing market

The rat retrosplenial cortex as a link for frontal functions: a lesion analysis

Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component

Effect of ultrasound and additives treatment as mitigation strategies to reduce acrylamide formation in potato crisps on industrial scale

The aim of this work was to examine the applicability on large scale of additives and ultrasound treatments during soaking of potatoes before frying to mitigate the formation of acrylamide in potato crisps. Calcium chloride and citric acid were applied at laboratory scale in various concentrations and orders during washing before frying, to establish optimum conditions which were scaled up to pilot plant. Up to 91.0% reduction in acrylamide was obtained at laboratory scale. Both concentration and order of additives influenced the extent of the mitigation observed, with a higher concentration of additive in the second wash being beneficial. When upscaled to factory pilot plant, the reduction observed was not consistent across the three trials, with a 33.4% reduction in the first trial but no significant reduction in following studies. A 2-min ultrasound treatment was applied in two trials to test various powers and amplitudes, and washing combinations respectively. Up to 67.1% of acrylamide reduction was recorded after 2 min of ultrasound treatment in the cold wash followed by hot wash; however, ultrasound treatment was not effective in reducing acrylamide or its precursors when solely applied or when followed by cold wash under the tested conditions of duration and power

Lack of change in CA1 dendritic spine density or clustering in rats following training on a radial-arm maze task [version 2; peer review: 2 approved]

Background: Neuronal plasticity is thought to underlie learning and memory formation. The density of dendritic spines in the CA1 region of the hippocampus has been repeatedly linked to mnemonic processes. Both the number and spatial location of the spines, in terms of proximity to nearest neighbour, have been implicated in memory formation. To examine how spatial training impacts synaptic structure in the hippocampus, Lister-Hooded rats were trained on a hippocampal-dependent spatial task in the radial-arm maze. Methods: One group of rats were trained on a hippocampal-dependent spatial task in the radial arm maze. Two further control groups were included: a yoked group which received the same sensorimotor stimulation in the radial-maze but without a memory load, and home-cage controls. At the end of behavioural training, the brains underwent Golgi staining. Spines on CA1 pyramidal neuron dendrites were imaged and quantitatively assessed to provide measures of density and distance from nearest neighbour. Results: There was no difference across behavioural groups either in terms of spine density or in the clustering of dendritic spines. Conclusions: Spatial learning is not always accompanied by changes in either the density or clustering of dendritic spines on the basal arbour of CA1 pyramidal neurons when assessed using Golgi imaging

Operational considerations for hot-washing in potato crisp manufacture

As part of an overall programme aimed at reducing the acrylamide content of crisps, this paper explores the impact of hot-washing on potato slice sugar concentration during industrial scale manufacture. We investigated cold-washing as an alternative to hot-washing, hot-wash residence time and temperature to optimise sugar removal and therefore reduce the potential for high acrylamide levels after frying. Due to the variable nature of potatoes, an extensive variability study was performed to determine confidence boundaries of results. It was found that the cold-wash unit removed on average 21% of the initial sugar content. In the hot-wash the current operational residence time of 3.5 minutes at 70oC gave a sugar reduction of 27.5%, which could be increased to 48.5% if residence time is extended to 5 minutes. Hot-wash temperatures of 40oC - 60oC were found to increase glucose and fructose content and therefore the potential for acrylamide formation. A “double cold-wash” was trialled and proved to be as successful as hot-washing at 70oC for all but the highest sugar potatoes, challenging the current operational process and offering the potential for major energy savings

Fryer control strategy improvement:towards acrylamide reduction in crisp manufacture

This paper describes research efforts to improve the operation of industrial scale crisp fryers to ensure that product quality targets are exceeded. The work described was undertaken within a project whose aim is to minimise the acrylamide formation arising during processing operations. The existing fryer temperature control scheme was found to be sub-optimal from an acrylamide perspective and involved considerable operator intervention, particularly at fryer start-up. A new temperature control system was designed and implemented to overcome the shortcomings of the existing strategy. Fryer temperature and crisp moisture were regulated effectively through gas flow and dwell time modifications. Interactions between loops were compensated for and start-up was automated to reduce the impact of operator-to-operator variation. The resulting scheme was found to deliver much-improved temperature control which will lead to a resultant decrease in acrylamide formation

Uptake of synthetic low density lipoprotein by leukemic stem cells — a potential stem cell targeted drug delivery strategy

Chronic Myeloid Leukemia (CML) stem/progenitor cells, which over-express Bcr-Abl, respond to imatinib by a reversible block in proliferation without significant apoptosis. As a result, patients are unlikely to be cured owing to the persistence of leukemic quiescent stem cells (QSC) capable of initiating relapse. Previously, we have reported that intracellular levels of imatinib in primary primitive CML cells (CD34<sup>+</sup>38<sup>lo/−</sup>), are significantly lower than in CML progenitor cells (total CD34<sup>+</sup>) and leukemic cell lines. The aim of this study was to determine if potentially sub-therapeutic intracellular drug concentrations in persistent leukemic QSC may be overcome by targeted drug delivery using synthetic Low Density Lipoprotein (sLDL) particles. As a first step towards this goal, however, the extent of uptake of sLDL by leukemic cell lines and CML patient stem/progenitor cells was investigated. Results with non-drug loaded particles have shown an increased and preferential uptake of sLDL by Bcr-Abl positive cell lines in comparison to Bcr-Abl negative. Furthermore, CML CD34<sup>+</sup> and primitive CD34<sup>+</sup>38<sup>lo/−</sup> cells accumulated significantly higher levels of sLDL when compared with non-CML CD34<sup>+</sup> cells. Thus, drug-loading the sLDL nanoparticles could potentially enhance intracellular drug concentrations in primitive CML cells and thus aid their eradication

Immunomics-guided antigen discovery for praziquantel-induced vaccination inurogenital human schistosomiasis

Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis

Growth reference charts for children with hypochondroplasia

Hypochondroplasia (HCH) is a rare skeletal dysplasia causing mild short stature. There is a paucity of growth reference charts for this population. Anthropometric data were collected to generate height, weight, and head circumference (HC) growth reference charts for children with a diagnosis of HCH. Mixed longitudinal anthropometric data and genetic analysis results were collected from 14 European specialized skeletal dysplasia centers. Growth charts were generated using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were collected from 188 (79 female) children with a diagnosis of HCH aged 0-18 years. Of the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). The data were used to generate growth references for height, weight, and HC, plotted as charts with seven centiles from 2nd to 98th, for ages 0-4 and 0-16 years. HCH-specific growth charts are important in the clinical care of these children. They help to identify if other comorbidities are present that affect growth and development and serve as an important benchmark for any prospective interventional research studies and trials