The emergence of the brain non-CpG methylation system in vertebrates

Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett Syndrome. However, it is unclear if the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distant animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. Concomitantly, we found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage

The dental calculus metabolome in modern and historic samples.

INTRODUCTION: Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. OBJECTIVE: We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss. RESULTS: Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples. CONCLUSIONS: The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies

Dental metric standards for sex estimation in archaeological populations from Iran

Sex estimation of skeletal remains is one of the major components of forensic identification of unknown individuals. Teeth are a potential source of information on sex and are often recovered in archaeological or forensic contexts due to their post-mortem longevity. Currently there is limited data on dental sexual dimorphism of archaeological populations from Iran. This dissertation represents the first study to provide a dental sex estimation method for Iron Age populations. The current study was conducted on the skeletal remains of 143 adults from two Iron Age populations in close temporal and geographic proximity in the Solduz Valley (West Azerbaijan Province of Iran). 2D and 3D cervical mesiodistal and buccolingual and root volume measurements of maxillary and mandibular teeth were used to investigate the degree of sexual dimorphism in permanent dentition and to assess their applicability in sex estimation. In total 1327, 457, and 480 anterior and posterior teeth were used to collect 2D cervical, 3D cervical, and root volume measurements respectively. 2D cervical measurements were taken using Hillson-Fitzgerald dental calliper and 3D measurements were collected using CT images provided by Open Research Scan Archive (ORSA) - Penn Museum. 3D models of the teeth were created using manual segmentation in the Amira 6.01 software package. Since tooth density largely differs from crown to apex, root segmentation required two threshold levels: the segmentation of the root from the jaw and the segmentation of the crown from the root. Thresholds used for root segmentation were calculated using the half maximum height protocol of Spoor et al. (1993) for each skull, and thresholds used for crown segmentation were set visually for each tooth separately. Data was analysed using discriminant function analysis and posterior probabilities were calculated for all produced formulae where sex was previously assessed from morphological features of pelvis and skull. Bootstrapping was used to account for small sample sizes in the analysis. Statistical analysis was carried out using SPSS 23. The percentage of sexual dimorphism was also used to quantify the amount of sexual dimorphism in the sample. The results showed that incisors and canines were the most sexually dimorphic teeth, providing percentages of correct sex classification between 80% and 100% depending on the measurement used. Root volume measurement was shown to be the most sexually dimorphic variable providing an accuracy of over 90% in all functions. The present study provided the first dental metric standards for sex estimation using odontometric data in Iranian archaeological populations. Dental measurements, particularly root volume measurements, were found to be of value for sex assessment and the method presented here could be a useful tool for establishing accurate demographic data from skeletal remains of the Iron Age from Iran

A single-cell atlas of entorhinal cortex from individuals with Alzheimer's disease reveals cell-type-specific gene expression regulation

10.1038/s41593-019-0539-4NATURE NEUROSCIENCE22122087-209

A comparison of three established age estimation methods on an adult Spanish sample.

Most current methods for adult skeletal age-at-death estimation are based on American samples comprising individuals of European and African ancestry. Our limited understanding of population variability hampers our efforts to apply these techniques to various skeletal populations around the world, especially in global forensic contexts. Further, documented skeletal samples are rare, limiting our ability to test our techniques. The objective of this paper is to test three pelvic macroscopic methods (1-Suchey-Brooks; 2- Lovejoy; 3- Buckberry and Chamberlain) on a documented modern Spanish sample. These methods were selected because they are popular among Spanish anthropologists and because they never have been tested in a Spanish sample. The study sample consists of 80 individuals (55 ♂ and 25 ♀) of known sex and age from the Valladolid collection. Results indicate that in all three methods, levels of bias and inaccuracy increase with age. The Lovejoy method performs poorly (27%) compared with Suchey-Brooks (71%) and Buckberry and Chamberlain (86%). However, the levels of correlation between phases and chronological ages are low and comparable in the three methods (< 0.395). The apparent accuracy of the Suchey-Brooks and Buckberry and Chamberlain methods is largely based on the broad width of the methods" estimated intervals. This study suggests that before systematic application of these three methodologies in Spanish populations, further statistical modeling and research into the co-variance of chronological age with morphological change is necessary. Future methods should be developed specific to various world populations, and should allow for both precision and flexibility in age estimation

Degenerative changes of the sacroiliac auricular joint surface?validation of influential factors

The purpose of this study was to clarify the relevance of degenerative changes in the sacroiliac joint (SIJ) and the joints in the lower limb and lumbar spine using age estimation methods. We also examined the shape of the auricular surface to determine the effect of degenerative changes on each joint. A total of 200 iliac auricular surfaces from 100 Japanese male skeletons were examined macroscopically in accordance with conventional methods of age estimation. From the obtained estimated age, we calculated the deflection values, which represented the degree of degenerative changes of the joints. For comparison, we used osteophyte score data of the hip, knee, and zygapophyseal joints in lumbar spines from previous studies which had used the same bone specimens. As a quantitative indicator of auricular surface morphology, we defined the constriction ratio (CR) of the auricular surface and compared the CR values obtained with various measured values. Degenerative changes in the SIJ were positively correlated with those in both the hip joint and zygapophyseal joint, but a correlation with knee joints was found only on the left side. In skeletons from individuals aged ?60 years as time of death, the CR was significantly different between the group with high scores and those with low scores in both the hip and sacroiliac joints. It has been suggested that degenerative changes in SIJs interact with those in the hip joint and zygapophyseal joint. In addition, the shape of the auricular surface may also be a relevant factor for degenerative changes in these joints

Anglo-Saxon concepts of dis/ability: Placing disease at Great Chesterford in its wider context

Within Anglo-Saxon society, individuals obtained their status on the basis of their ability to undertake required and prescribed social roles. People experiencing impairment, be that as a result of disease or some other process including trauma or pregnancy, might thus have reduced ability to undertake socially required activities. These people would have been highly visible within contemporary society by their very inability to undertake all required roles. These ideas are explored using a cluster of inhumations from the early Anglo-Saxon cemetery at Great Chesterford. Cemetery topography, visibility of difference, liminality, and etiology are explored in order to suggest the importance of the development of a sample-based approach to osteobiography. These might then be used to establish local understandings of disability,whereby individuals are viewed as people with focus placed on ability

Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage

Background: Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates. Results: Metagenomic data was generated from modern and historic calculus samples, and dental plaque metagenomic data was downloaded from the Human Microbiome Project. Microbial composition and functional profile were assessed. Metaproteomic data was obtained from a subset of historic calculus samples. Comparisons between microbial, protein, and metabolomic profiles revealed distinct taxonomic and metabolic functional profiles between plaque, modern calculus, and historic calculus, but not between calculus collected from healthy teeth and periodontal disease-affected teeth. Species co-exclusion was related to biofilm environment. Proteomic profiling revealed that healthy tooth samples contain low levels of bacterial virulence proteins and a robust innate immune response. Correlations between proteomic and metabolomic profiles suggest co-preservation of bacterial lipid membranes and membrane-associated proteins. Conclusions: Overall, we find that there are systematic microbial differences between plaque and calculus related to biofilm physiology, and recognizing these differences is important for accurate data interpretation in studies comparing dental plaque and calculus.</p