Separation and properties of human brain hexosaminidase C

Hexosaminidase C was separated from human brain supernatant by immunoadsorption of the A and B forms on to a column of immobilized antibody followed by preparative starch-block electrophoresis. There were some differences in the properties of hexosaminidase C preparations after each of these stages, shown by comparison of their heat-inactivation characteristics and filtration through Bio-Gel P-200. The C form prepared by both separation steps had properties which differed markedly from those of the A and B isoenzymes; its molecular weight was much larger, greater than 200000, it had optimum activity between pH6 and 7 and could not be successfully eluted from DEAE-cellulose, even with high salt concentrations, or from Sephadex G-200. These results seem to support the proposal that the C form is under a separate genetic control from the others.     

Metabolism of 35S-labelled Antithyroid Drugs in Man

Differences in the metabolic fate of antithyroid drugs influence the optimal frequency of administration and their therapeutic efficacy. ³⁵S propylthiouracil differed from the ³⁵S imidazoles (carbimazole and methimazole) in the more rapid absorption and excretion and the shorter biological half-life in the plasma of the former. Renal function may have a more important influence on the biological half-life of the drugs than thyroid status. Further work is required to determine the optimal frequency of administration for each compound.     

Use of nuclear morphometry characteristics to distinguish between normal and abnormal cervical glandular histologies.

This is a methodological study exploring the use of quantitative histopathology applied to the cervix to discriminate between normal and cancerous (consisting of adenocarcinoma and adenocarcinoma in situ) tissue samples. The goal is classifying tissue samples, which are populations of cells, from measurements on the cells. Our method uses one particular feature, the IODs-Index, to create a tissue level feature. The specific goal of this study is to find a threshold for the IODs-Index that is used to create the tissue level feature. The main statistical tool is Receiver Operating Characteristic (ROC) curve analysis. When applied to the data, our method achieved promising results with good estimated sensitivity and specificity for our data set. The optimal threshold for the IODs-Index was found to be 2.12.     

An aetiological study of 290 XXY males,with special reference to the role of paternal age

Summary Data on 290 non-mosaic 47,XXY males have been analysed for possible associations with parental ages at birth, season of birth, sex ratio among sibs, and twinning. Comparison with matched population controls revealed a highly significant association with parental age, which was fully explained by dependence on maternal age and maternal age alone. The maternal age effect was determined with greater precision than in an earlier study of the same material, in which siblings were used as controls, and was estimated to result in an increased risk of between 5% and 10% per annum (p.a.). The estimated independent effect of paternal age, after fitting maternal age, was marginally (but not significantly) negative, and excluded an increased risk in excess of 3% p.a. Paternal age therefore appears to have little if any independent significance in the aetiology of 47,XXY. After correcting for seasonal variations in the population birth rate and smoothing, there was a peak of XXY births in March and a trough in November. Though not statistically significant, the pattern resembled that reported in previous studies, and was similar for both younger and older mothers. The twinning rate for both the XXYs and their sibs, and the sex ratio among the latter, were close to the corresponding population values.     

Fruit-coat and seed fats of Rhopalostylis, Elaeocarpus and Nestegis species

The fruit-coat fats of Rhopalostylis sapida, R. baueri (Palmae), Elaeocarpus dentatus (Elaeocarpaceae) and Nestegis cunninghamii (Oleaceae) and the seed fats of E. dentatus and N. cunninghamii contain as their major fatty acids palmitic 11–35%, oleic 13–68%, and linoleic 16–31%. The seed fat of E. dentatus contains 10% hexadecenoic acid and the fruit-coat fat of N. cunninghamii 13% linolenic acid.     

Functional Modulation of the Glutamate Transporter Variant GLT1b by the PDZ Domain Protein PICK1

The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulatory effect on trafficking of AMPA-type glutamate receptors. The 11 extreme C-terminal residues specific for the GLT1b variant are essential for its specific interaction with the PICK1 PDZ domain, but a functional consequence of this interaction has remained unresolved. To identify a functional effect of PICK1 on GLT1a or GLT1b separately, we employed the Xenopus laevis expression system. GLT1a and GLT1b displayed similar electrophysiological properties and EC₅₀ for glutamate. Co-expressed PICK1 localized efficiently to the plasma membrane and resulted in a 5-fold enhancement of the leak current in GLT1b-expressing oocytes with only a minor effect on [³H]glutamate uptake. Three different GLT1 substrates all caused a slow TBOA-sensitive decay in the membrane current upon prolonged application, which provides support for the leak current being mediated by GLT1b itself. Leak and glutamate-evoked currents in GLT1a-expressing oocytes were unaffected by PICK1 co-expression. PKC activation down-regulated GLT1a and GLT1b activity to a similar extent, which was not affected by co-expression of PICK1. In conclusion, PICK1 may not only affect glutamatergic neurotransmission by its regulatory effect on glutamate receptors but may also affect neuronal excitability via an increased GLT1b-mediated leak current. This may be particularly relevant in pathological conditions such as amyotrophic lateral sclerosis and cerebral hypoxia, which are associated with neuronal GLT1b up-regulation.     

Digest: Little evidence exists for a virulence‐transmission trade‐off*

Research predicting the impact and spread of infectious disease has been heavily influenced by the idea of an evolutionary trade‐off between a pathogen's virulence and its transmission rate. In a meta‐analysis of the key underlying relationships, Acevedo et al. (2019) highlight the surprising lack of empirical evidence for this influential hypothesis.     

Age-associated B cells in viral infection

Age-associated B cells (ABCs) are a recently identified, unique B cell population that displays both protective and pathogenic characteristics, depending on the context. A major role of ABCs is to protect from viral infection. ABCs expand during an array of viral infections and display various functional capacities, including secretion of antibodies and activation of T cells. Following resolution of infection, ABCs appear to persist and play a crucial role in memory and recall responses. Here, we review the currently understanding of ABCs in the antiviral response in both humans and mice. We discuss avenues for future research, including the impact of sex on the ABC population and heterogeneity of ABCs between contexts.