Anxiolysis and recognition memory enhancement with long-term supplemental ascorbic acid (vitamin C) in normal rats: possible dose dependency and sex differences

To investigate a possible dose-response relationship and sex differences for anxiolytic and memory-enhancing effects of ascorbic acid (vitamin C), an adult PVG /c hooded rats were individually treated for 8 weeks with approximately 61, 114 or 160 mg/kg/ day of ascorbic acid in their drinking water. After their treatment, over 3 consecutive days they experienced a 5-min trial in an open field (OF) followed by a 5-min trial in an elevated plus maze (EPM), and then finally a 5-min novel object recognition (NOR) test in the OF. Dose-related anxiolytic effects were observed that to some extent depended on the measure of anxiety. In other words, anxiolytic effects were evident in higher frequencies of walking with 114 mg/kg and 61 mg/kg, higher frequencies of rearing and lower frequencies of grooming in the OF as well as more frequent occupation of the EPM open arms. Rats treated with 160 mg/kg explored a novel versus familiar object in the NOR test to a significantly greater extent than control rats thereby suggesting enhancement of their recognition memory. Overall, it appeared that the anxiolytic effects of ascorbic acid were more typical of the lowest dose, whereas memory enhancement appeared to be confined to the highest dose. While there were a number of significant sex differences, there was no evidence of differences between females and males in the effects of ascorbic acid

Exclusion of the Locus for Autosomal Recessive Pseudohypoaldosteronism Type 1 from the Mineralocorticoid Receptor Gene Region on Human Chromosome 4q by Linkage Analysis.

Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocorticoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provdes evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families

A field and laboratory evaluation of a commercial ELISA for the detection of Giardia coproantigens in humans and dogs

A capture enzyme linked immunosorbent assay (ELISA®) was evaluated for its ability to detect Giardia coproantigens in the faeces of humans and dogs in the Perth metropolitan area and Aboriginal communities in Fitzroy Crossing, Western Australia. Using zinc sulphate flotation and light microscopy, Giardia cysts and/or trophozoites were observed in 8 of 57 (14%) human stool samples from Perth and 21 of 55 (38%) stool samples from Fitzroy Crossing, after 2 separate examinations. Analysis of diagnostic sensitivity using the ELISA revealed that coproantigens were detected in all 29 human samples (100%) in which Giardia cysts and/or trophozoites were also present. Coproantigens were detected in one further sample from Perth and in 3 samples from Fitzroy Crossing in which no Giardia cyst or trophozoite was observed. The specificity of the test, as defined using Fitzroy Crossing samples free from Giardia, was 91%. The assay did not crossr-eact with Giardia-free stool samples containing Hymenolepis nana, Entamoeba coli, E. hartmanni, Chilomastix mesnili or Ancylostoma duodenale. Giardia cysts and/or trophozoites were also observed in 11 of 32 dog faecal samples (34%) in Perth and 11 of 29 dog samples (38%) in Fitzroy Crossing, after one zinc sulphate examination. The sensitivity of the ELISA for dogs was 64% and 55% for Perth and Fitzroy Crossing specimens respectively. The specificity was 95% when Fitzroy Crossing samples were used. Other parasites observed in Giardia-free faecal samples from dogs which did not produce a positive reaction with the kit were Ancylostoma caninum, Sarcocystis sp. and Isospora sp. The assay was tested under field conditions, in Fitzroy Crossing, where the results were read visually and were shown to correlate well with results obtained using spectrophotometry. Giardia coproantigens present in human stools remained detectable by the ELISA even after storage untreated at 25 °C for 8

Post-training inactivation of the anterior thalamic nuclei impairs spatial performance on the radial arm maze

The limbic thalamus, specifically the anterior thalamic nuclei (ATN), contains brain signals including that of head direction cells, which fire as a function of an animal\u27s directional orientation in an environment. Recent work has suggested that this directional orientation information stemming from the ATN contributes to the generation of hippocampal and parahippocampal spatial representations, and may contribute to the establishment of unique spatial representations in radially oriented tasks such as the radial arm maze. While previous studies have shown that ATN lesions can impair spatial working memory performance in the radial maze, little work has been done to investigate spatial reference memory in a discrimination task variant. Further, while previous studies have shown that ATN lesions can impair performance in the radial maze, these studies produced the ATN lesions prior to training. It is therefore unclear whether the ATN lesions disrupted acquisition or retention of radial maze performance. Here, we tested the role of ATN signaling in a previously learned spatial discrimination task on a radial arm maze. Rats were first trained to asymptotic levels in a task in which two maze arms were consistently baited across training. After 24 h, animals received muscimol inactivation of the ATN before a 4 trial probe test. We report impairments in post-inactivation trials, suggesting that signals from the ATN modulate the use of a previously acquired spatial discrimination in the radial-arm maze. The results are discussed in relation to the thalamo-cortical limbic circuits involved in spatial information processing, with an emphasis on the head direction signal. © 2017 Harvey, Thompson, Sanchez, Yoder and Clark

Development of an acceptable and feasible self-management group for children, young people and families living with Type 1 diabetes.

AIMS: This study developed an acceptable and feasible self-management intervention that addresses the self-identified needs of children and young people with Type 1 diabetes and their parents. METHODS: Phase 1 reviewed previous interventions and interviewed the clinical team, young people and families. Phase 2 ran three age-matched focus groups with 11 families of children aged 8-16 years. Feedback was used to modify the workshop. Phase 3 evaluated feasibility of delivery, as well as the effects on metabolic control, quality of life and fear of hypoglycaemia, measured at baseline and 1-3 months post intervention. RESULTS: Eighty-nine families were invited to take part. Twenty-two (25%) participated in seven pilot groups (median age of young people 10 years, 36% girls). The intervention comprised a developmentally appropriate workshop for young people and parents addressing: (1) blood glucose control, (2) the potential impact of long-term high HbA1c , (3) the effects of 'hypos' and 'hypers', (4) self-management techniques and (5) talking confidently to people about diabetes. Participants were enthusiastic and positive about the workshop and would recommend it to others. Young people liked sharing ideas and meeting others with diabetes, while parents enjoyed listening to their children talk about their diabetes knowledge. CONCLUSIONS: Families living with Type 1 diabetes participated in developing a self-management group intervention. Although we demonstrated acceptability and feasibility, the pilot study results do not support the development of a randomized control trial to evaluate the effectiveness in improving HbA1c

A Quantum Bousso Bound

The Bousso bound requires that one quarter the area of a closed codimension two spacelike surface exceeds the entropy flux across a certain lightsheet terminating on the surface. The bound can be violated by quantum effects such as Hawking radiation. It is proposed that at the quantum level the bound be modified by adding to the area the quantum entanglement entropy across the surface. The validity of this quantum Bousso bound is proven in a two-dimensional large N dilaton gravity theory.Comment: 17 page

Complexation of novel thiomers and insulin to protect against in vitro enzymatic degradation: towards oral insulin delivery.

A significant barrier to oral insulin delivery is its enzymatic degradation in the gut. Nano-sized polymer-insulin polyelectrolyte complexes (PECS) have been developed to protect insulin against enzymatic degradation. Poly(allylamine) (Paa) was trimethylated to yield QPaa. Thiolation of Paa and QPaa was achieved by attaching either N-acetylcysteine (NAC), or thiobutylamidine (TBA) ligands (Paa-NAC/QPaa-NAC and Paa-TBA/QPaa-TBA thiomers). PEC formulations were prepared in Tris buffer (pH 7.4) at various polymer:insulin mass ratios (0.2:1-2:1). PECS were characterised by %transmittance of light and photon correlation spectroscopy. Insulin complexation efficiency and enzyme-protective effect of these complexes was determined by HPLC. Complexation with insulin was found to be optimal at mass ratios of 0.4-1:1 for all polymers. PECS in this mass range were positively-charged (20-40 mV), nanoparticles (50-200 nm), with high insulin complexation efficiency (> 90 %). Complexation with TBA polymers appeared to result in disulphide bridge formation between the polymers and insulin. In vitro enzymatic degradation assays of QPaa, Paa-NAC, and QPaa-NAC PECS showed that they all offered some protection against insulin degradation by trypsin and {esc}ga{esc}s-chymotrypsin, but not from pepsin. QPaa-NAC complexes with insulin are the most promising formulation for future work, given their ability to offer protection against intestinal enzymes. This work highlights the importance of optimising polymer structure in the delivery of proteins

Results from the adaptive optics coronagraph at the William Herschel Telescope

Described here is the design and commissioning of a coronagraph facility for the 4.2-m William Herschel Telescope (WHT) and its Nasmyth Adaptive Optics for Multi-purpose Instrumentation (NAOMI). The use of the NAOMI system gives an improved image resolution of 0.15 arcsec at a wavelength of 2.2 μm. This enables the Optimised Stellar Coronagraph for Adaptive optics (OSCA) to suppress stellar light using smaller occulting masks and thus allows regions closer to bright astronomical objects to be imaged. OSCA provides a selection of 10 different occulting masks with sizes of 0.25–2.0 arcsec in diameter, including two with full grey-scale Gaussian profiles. There is also a choice of different sized and shaped Lyot stops (pupil plane masks). Computer simulations of the different coronagraphic options with the NAOMI segmented mirror have relevance for the next generation of highly segmented extremely large telescopes