Is the biology of breast cancer changing? A study of hormone receptor status 1984-1986 and 1996-1997

Using archived tumours, those from 1984-1986 and 1996-1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival

DNA methylation is associated with codon degeneracy in a species of bumblebee

Social insects display extreme phenotypic differences between sexes and castes even though the underlying genome can be almost identical. Epigenetic processes have been proposed as a possible mechanism for mediating these phenotypic differences. Using whole genome bisulfite sequencing of queens, males, and reproductive female workers we have characterised the sex- and caste-specific methylome of the bumblebee Bombus terrestris. We have identified a potential role for DNA methylation in histone modification processes which may influence sex and caste phenotypic differences. We also find differentially methylated genes generally show low levels of DNA methylation which may suggest a separate function for lowly methylated genes in mediating transcriptional plasticity, unlike highly methylated genes which are usually involved in housekeeping functions. We also examined the relationship between the underlying genome and the methylome using whole genome re-sequencing of the same queens and males. We find DNA methylation is enriched at zero-fold degenerate sites. We suggest DNA methylation may be acting as a targeted mutagen at these sites, providing substrate for selection via non-synonymous changes in the underlying genome. However, we did not see any relationship between DNA methylation and rates of positive selection in our samples. In order to fully assess a possible role for DNA methylation in adaptive processes a specifically designed study using natural population data is needed.</p

The Explication Defence of Arguments from Reference

In a number of influential papers, Machery, Mallon, Nichols and Stich have presented a powerful critique of so-called arguments from reference, arguments that assume that a particular theory of reference is correct in order to establish a substantive conclusion. The critique is that, due to cross-cultural variation in semantic intuitions supposedly undermining the standard methodology for theorising about reference, the assumption that a theory of reference is correct is unjustified. I argue that the many extant responses to Machery et al.’s critique do little for the proponent of an argument from reference, as they do not show how to justify the problematic assumption. I then argue that it can in principle be justified by an appeal to Carnapian explication. I show how to apply the explication defence to arguments from reference given by Andreasen (for the biological reality of race) and by Churchland (against the existence of beliefs and desires)

Exploring the ageing methylome in the model insect, Nasonia vitripennis

Background: The ageing process is a multifaceted phenomenon marked by the gradual deterioration of cellular and organismal functions, accompanied by an elevated susceptibility to diseases. The intricate interplay between genetic and environmental factors complicates research, particularly in complex mammalian models. In this context, simple invertebrate organisms have been pivotal, but the current models lack detectable DNA methylation limiting the exploration of this critical epigenetic ageing mechanism. This study introduces Nasonia vitripennis, the jewel wasp, as an innovative invertebrate model for investigating the epigenetics of ageing. Leveraging its advantages as a model organism and possessing a functional DNA methylation system, Nasonia emerges as a valuable addition to ageing research. Results: Whole-genome bisulfite sequencing unveiled dynamic alterations in DNA methylation, with differentially methylated CpGs between distinct time points in both male and female wasps. These changes were associated with numerous genes, enriching for functions related to telomere maintenance, histone methylation, and mRNA catabolic processes. Additionally, other CpGs were found to be variably methylated at each timepoint. Sex-specific effects on epigenetic entropy were observed, indicating differential patterns in the loss of epigenetic stability over time. Constructing an epigenetic clock containing 19 CpGs revealed a robust correlation between epigenetic age and chronological age. Conclusions: Nasonia vitripennis emerges as a promising model for investigating the epigenetics of ageing, shedding light on the intricate dynamics of DNA methylation and their implications for age-related processes. This research not only expands the repertoire of ageing models but also opens avenues for deeper exploration of epigenetic mechanisms in the context of ageing

Development of a framework for genotyping bovine-derived Cryptosporidium parvum, using a multilocus fragment typing tool

Background: There is a need for an integrated genotyping approach for C. parvum; no sufficiently discriminatory scheme to date has been fully validated or widely adopted by veterinary or public health researchers. Multilocus fragment typing (MLFT) can provide good differentiation and is relatively quick and cheap to perform. A MLFT tool was assessed in terms of its typeability, specificity, precision (repeatability and reproducibility), accuracy and ability to genotypically discriminate bovine-derived Cryptosporidium parvum. Methods: With the aim of working towards a consensus, six markers were selected for inclusion based on their successful application in previous studies: MM5, MM18, MM19, TP14, MS1 and MS9. Alleles were assigned according to the fragment sizes of repeat regions amplified, as determined by capillary electrophoresis. In addition, a region of the GP60 gene was amplified and sequenced to determine gp60 subtype and this was added to the allelic profiles of the 6 markers to determine the multilocus genotype (MLG). The MLFT tool was applied to 140 C. parvum samples collected in two cross-sectional studies of UK calves, conducted in Cheshire in 2004 (principally dairy animals) and Aberdeenshire/Caithness in 2011 (beef animals). Results: Typeability was 84 %. The primers did not amplify tested non-parvum species frequently detected in cattle. In terms of repeatability, within- and between-run fragment sizes showed little variability. Between laboratories, fragment sizes differed but allele calling was reproducible. The MLFT had good discriminatory ability (Simpson’s Index of Diversity, SID, was 0.92), compared to gp60 sequencing alone (SID 0.44). Some markers were more informative than others, with MS1 and MS9 proving monoallelic in tested samples. Conclusions: Further inter-laboratory trials are now warranted with the inclusion of human-derived C. parvum samples, allowing progress towards an integrated, standardised typing scheme to enable source attribution and to determine the role of livestock in future outbreaks of human C. parvum

Measurement properties of the Minimal Insomnia Symptom Scale (MISS) in an elderly population in Sweden

<p>Abstract</p> <p>Background</p> <p>Insomnia is common among elderly people and associated with poor health. The Minimal Insomnia Symptom Scale (MISS) is a three item screening instrument that has been found to be psychometrically sound and capable of identifying insomnia in the general population (20-64 years). However, its measurement properties have not been studied in an elderly population. Our aim was to test the measurement properties of the MISS among people aged 65 + in Sweden, by replicating the original study in an elderly sample.</p> <p>Methods</p> <p>Data from a cross-sectional survey of 548 elderly individuals were analysed in terms of assumptions of summation of items, floor/ceiling effects, reliability and optimal cut-off score by means of ROC-curve analysis and compared with self-reported insomnia criteria.</p> <p>Results</p> <p>Corrected item-total correlations ranged between 0.64-0.70, floor/ceiling effects were 6.6/0.6% and reliability was 0.81. ROC analysis identified the optimal cut-off score as ≥7 (sensitivity, 0.93; specificity, 0.84; positive/negative predictive values, 0.256/0.995). Using this cut-off score, the prevalence of insomnia in the study sample was 21.7% and most frequent among women and the oldest old.</p> <p>Conclusions</p> <p>Data support the measurement properties of the MISS as a possible insomnia screening instrument for elderly persons. This study make evident that the MISS is useful for identifying elderly people with insomnia-like sleep problems. Further studies are needed to assess its usefulness in identifying clinically defined insomnia.</p