Short- and long-term effects of 56Fe irradiation on cognition and hippocampal DNA methylation and gene expression.

BackgroundAstronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously that object recognition requiring the hippocampus, a structure critical for cognitive function, is affected in 2-month-old mice irradiated with 56Fe ions. Here we examined object recognition in 6-month-old mice irradiated with 56Fe ions, a biological age more relevant to the typical ages of astronauts. Moreover, because the mechanisms mediating the detrimental effects of 56Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression. We assessed the effects of whole body 56Fe ion irradiation at early (2 weeks) and late (20 weeks) time points on hippocampus-dependent memory and hippocampal network stability, and whether these effects are associated with epigenetic changes in hippocampal DNA methylation (both 5mC and 5hmC) and gene expression.ResultsAt the two-week time point, object recognition and network stability were impaired following irradiation at the 0.1 and 0.4 Gy dose, but not following irradiation at the 0.2 Gy dose. No impairments in object recognition or network stability were seen at the 20-week time point at any irradiation dose used. Consistent with this pattern, the significance of pathways for gene categories for 5hmC was lower, though not eliminated, at the 20-week time point compared to the 2-week time point. Similarly, significant changes were observed for 5mC gene pathways at the 2-week time point, but no significant gene categories were observed at the 20-week time point. Only the 5hmC changes tracked with gene expression changes.ConclusionsDose- and time-dependent epigenomic remodeling in the hippocampus following 56Fe ion exposure correlates with behavioral changes

Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis.

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility

Form, science, and narrative in the anthropocene

A significant strand of contemporary fiction engages with scientific models that highlight a constitutive interdependency between humanity and material realities such as the climate or the geological history of our planet. This article looks at the ways in which narrative may capture this human-nonhuman interrelation, which occupies the foreground of debates on the so-called Anthropocene. I argue that the formal dimension of scientific knowledge-as manifested by diagrams or metaphors used by scientists-is central to this narrative remediation. I explore two analogical strategies through which narrative may pursue a formal dialogue with science: clusters of metaphorical language and the global structuring of the plot. Rivka Galchen's novel Atmospheric Disturbances (2008), for instance, builds on a visual representation of meteorological patterns in a storm (lifted from an actual scientific paper) to stage the narrator's mental illness. Two other contemporary works (Orfeo by Richard Powers and A Tale for the Time Being by Ruth Ozeki) integrate scientific models through the overall design of the plot. By offering close readings of these novels, I seek to expand work in the area of New Formalism and show how formal choices are crucial to bringing together the human-scale world and more-than-human phenomena

Cognitive Bias in Line-Up Identifications: The Impact of Administrator Knowledge

Prior knowledge of the likely or expected outcome of a forensic investigation has been shown to produce biases in the results obtained, reducing objectivity. The wide prevalence of such cognitive biases in many judgments has long been recognised by social psychologists, but its importance is only now gaining appreciation within forensic science communities. It is therefore timely to draw attention to the power of cognitive biases found in a study of the influence of administrator expectations on photographic identifications. Data are presented to show that when a line-up administrator knows the identity and position of a target within a line-up choice, in which the ‘witness’ is ignorant of the actual target, that target is more than twice as likely to be selected compared with when the administrator is kept ‘blind’. These findings, taken together with related studies, support the recommendation that all forensic analyses are made ‘double-blind’—a method that has proven to be effective in reducing such effects within the social sciences

Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy

Background: DNA methylation is an essential epigenetic mark, controlled by DNA methyltransferase (DNMT) proteins, which regulates chromatin structure and gene expression throughout the genome. In this study, we describe a family with adult-onset autosomal dominant cerebellar ataxia with deafness and narcolepsy (ADCA-DN) caused by mutations in the maintenance methyltransferase DNMT1 and assess the DNA methylation profile of these individuals. Results: We report a family with six individuals affected with ADCA-DN; specifically, patients first developed hearing loss and ataxia, followed by narcolepsy, and cognitive decline. We identified a heterozygous DNMT1 variant, c.1709C\u3eT [p.Ala570Val] by Sanger sequencing, which had been previously reported as pathogenic for ADCA-DN and segregated with disease in the family. DNA methylation analysis by high-resolution genome-wide DNA methylation array identified a decrease in CpGs with 0–10 % methylation and 80–95 % methylation and a concomitant increase in sites with 10–30 % methylation and \u3e95 % methylation. This pattern suggests an increase in methylation of normally unmethylated regions, such as promoters and CpG islands, as well as further methylation of highly methylated gene bodies and intergenic regions. Furthermore, a regional analysis identified 82 hypermethylated loci with consistent robust differences across ≥5 consecutive probes compared to our large reference cohort. Conclusions: This report identifies robust changes in the DNA methylation patterns in ADCA-DN patients, which is an important step towards elucidating disease pathogenesis

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

The Influence of Regret Proneness, Evidence Strengthening, and Perceived Responsibility on Verdict Preference

In the present study, we investigated perceived responsibility, evidence strengthening, and defendant gender in the context of a criminal trial involving DNA. Evidence was introduced post-trial and varied as strengthening the defendant’s guilt v. innocence. We also examined perceptions of perceived responsibility for verdict in order to more closely evaluate the role of regret in decision-making. Results indicated that DNA evidence is perceived as reliable, regardless of whether it strengthened guilt or innocence. In addition, greater confidence in verdict was observed when evidence strengthened the guilt of a female defendant vs. a male defendant. Finally, jurors experiencing high levels of regret perceived DNA evidence more selectively compared to jurors with low levels of regret, supporting the importance of identifying individual difference factors prior to trial

Why Biology is Beyond Physical Sciences?

In the framework of materialism, the major attention is to find general organizational laws stimulated by physical sciences, ignoring the uniqueness of Life. The main goal of materialism is to reduce consciousness to natural processes, which in turn can be translated into the language of math, physics and chemistry. Following this approach, scientists have made several attempts to deny the living organism of its veracity as an immortal soul, in favor of genes, molecules, atoms and so on. However, advancement in various fields of biology has repeatedly given rise to questions against such a denial and has supplied more and more evidence against the completely misleading ideological imposition that living entities are particular states of matter. In the recent past, however, the realization has arisen that cognitive nature of life at all levels has begun presenting significant challenges to the views of materialism in biology and has created a more receptive environment for the soul hypothesis. Therefore, instead of adjudicating different aprioristic claims, the development of an authentic theory of biology needs both proper scientific knowledge and the appropriate tools of philosophical analysis of life. In a recently published paper the first author of present essay made an attempt to highlight a few relevant developments supporting a sentient view of life in scientific research, which has caused a paradigm shift in our understanding of life and its origin [1]. The present essay highlights the uniqueness of biological systems that offers a considerable challenge to the mainstream materialism in biology and proposes the Vedāntic philosophical view as a viable alternative for development of a biological theory worthy of life

Public understanding of science and common sense: Social representations of the human microbiome among the expert and non-expert public

The aim of this investigation is to examine the structure and the content of different social groups’ representations of the human microbiome. We employed a non-probabilistic sample comprising two groups of participants. The first group (n = 244) included university students. The second group included lay people (n = 355). We chose a mixed-method approach. The data obtained were processed using IRaMuTeQ software. The results allow us to identify the anchoring and objectification processes activated by the two different groups of interviewees. The results could be useful to those in charge of implementing campaigns aimed at promoting health literac