Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

The Oldest Case of Decapitation in the New World (Lapa do Santo, East-Central Brazil)

We present here evidence for an early Holocene case of decapitation in the New World (Burial 26), found in the rock shelter of Lapa do Santo in 2007. Lapa do Santo is an archaeological site located in the Lagoa Santa karst in east-central Brazil with evidence of human occupation dating as far back as 11.7-12.7 cal kyBP (95.4% interval). An ultra-filtered AMS age determination on a fragment of the sphenoid provided an age range of 9.1-9.4 cal kyBP (95.4% interval) for Burial 26. The interment was composed of an articulated cranium, mandible and first six cervical vertebrae. Cut marks with a v-shaped profile were observed in the mandible and sixth cervical vertebra. The right hand was amputated and laid over the left side of the face with distal phalanges pointing to the chin and the left hand was amputated and laid over the right side of the face with distal phalanges pointing to the forehead. Strontium analysis comparing Burial 26's isotopic signature to other specimens from Lapa do Santo suggests this was a local member of the group. Therefore, we suggest a ritualized decapitation instead of trophy-taking, testifying for the sophistication of mortuary rituals among hunter-gatherers in the Americas during the early Archaic period. In the apparent absence of wealth goods or elaborated architecture, Lapa do Santo's inhabitants seemed to use the human body to express their cosmological principles regarding death

Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes

We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains—Dominance, Sociability, and Neuroticism—were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.

Data and code availability. RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. All code has been deposited in a publicly available GitHub Repository and an unchanging archive of this repository was created in Zenodo. Links to both repositories are listed in the key resources table Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.This is the final version. Available from Cell Press via the DOI in this record. Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.National Institutes of HealthNational Science FoundationNational Institute of Mental Healt

Individual Facial Coloration in Male Eulemur fulvus rufus: A Condition-dependent Ornament?

Researchers studying individual variation in conspicuous skin coloration in primates have suggested that color indicates male quality. Although primate fur color can also be flamboyant, the potential condition dependence and thus signaling function of fur remains poorly studied. We studied sources of variation in sexually dichromatic facial hair coloration in red-fronted lemurs (Eulemur fulvus rufus). We collected data on 13 adult males in Kirindy Forest, Madagascar, during two study periods in 2006 and 2007, to determine whether variation in facial hair coloration correlates with male age, rank, androgen status, and reproductive success. We quantified facial hair coloration via standardized digital photographs of each male, assessed androgen status using fecal hormone measurements, and obtained data on reproductive success through genetic paternity analyses. Male facial hair coloration showed high individual variation, and baseline coloration was related to individual androgen status but not to any other parameter tested. Color did not reflect rapid androgen changes during the mating season. However, pronounced long-term changes in androgen levels between years were accompanied by changes in facial hair coloration. Our data suggest that facial hair coloration in red-fronted lemur males is under proximate control of androgens and may provide some information about male quality, but it does not correlate with dominance rank or male reproductive success

Social connections predict brain structure in a multidimensional free-ranging primate society

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data, code, and materials used in this study are available on the Open Science Framework platform (osf.io). Link: https://osf.io/xfz3r/?view_only=66633a9490e649038330a98788a0cca3. Original brain tissue samples can be provided by the University of Pennsylvania pending scientific review and a completed material transfer agreement. Requests for brain tissues should be submitted to: [email protected] and survival in most primate species reflects management of both competitive and cooperative relationships. Here, we investigated the links between neuroanatomy and sociality in free-ranging rhesus macaques. In adults, the number of social partners predicted the volume of the mid-superior temporal sulcus and ventral-dysgranular insula, implicated in social decision-making and empathy, respectively. We found no link between brain structure and other key social variables such as social status or indirect connectedness in adults, nor between maternal social networks or status and dependent infant brain structure. Our findings demonstrate that the size of specific brain structures varies with the number of direct affiliative social connections and suggest that this relationship may arise during development. These results reinforce proposed links between social network size, biological success, and the expansion of specific brain circuits

ICAR: endoscopic skull‐base surgery

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The Role of Proteasome Beta Subunits in Gastrin-Mediated Transcription of Plasminogen Activator Inhibitor-2 and Regenerating Protein1

The hormone gastrin physiologically regulates gastric acid secretion and also contributes to maintaining gastric epithelial architecture by regulating expression of genes such as plasminogen activator inhibitor 2 (PAI-2) and regenerating protein 1(Reg1). Here we examine the role of proteasome subunit PSMB1 in the transcriptional regulation of PAI-2 and Reg1 by gastrin, and its subcellular distribution during gastrin stimulation. We used the gastric cancer cell line AGS, permanently transfected with the CCK2 receptor (AGS-GR) to study gastrin stimulated expression of PAI-2 and Reg1 reporter constructs when PSMB1 was knocked down by siRNA. Binding of PSMB1 to the PAI-2 and Reg1 promoters was assessed by chromatin immunoprecipitation (ChIP) assay. Subcellular distribution of PSMB1 was determined by immunocytochemistry and Western Blot. Gastrin robustly increased expression of PAI-2 and Reg1 in AGS-GR cells, but when PSMB1 was knocked down the responses were dramatically reduced. In ChIP assays, following immunoprecipitation of chromatin with a PSMB1 antibody there was a substantial enrichment of DNA from the gastrin responsive regions of the PAI-2 and Reg1 promoters compared with chromatin precipitated with control IgG. In AGS-GR cells stimulated with gastrin there was a significant increase in the ratio of nuclear:cytoplasmic PSMB1 over the same timescale as recruitment of PSMB1 to the PAI-2 and Reg1 promoters seen in ChIP assays. We conclude that PSMB1 is part of the transcriptional machinery required for gastrin stimulated expression of PAI-2 and Reg1, and that its change in subcellular distribution in response to gastrin is consistent with this role