Uruk expansion or integrated development? A petrographic and geochemical perspective from Gurga Chiya, Iraqi Kurdistan

The Late Chalcolithic (LC; c.4500-3100BCE) was an important period in the developmental history of ancient Mesopotamia (modern Iraq, north-eastern Syria and south-eastern Turkey). New forms of socio-political and economic organisation are observed, characterised by household/settlement hierarchies, centralised production, craft specialization and redistribution. The Uruk Phenomenon of the latter 4th millennium BCE (LC3-5 in northern Mesopotamia and Middle-Late Uruk Period in southern Mesopotamia) coincides with the world’s first urban societies in northern and southern Mesopotamia. This phenomenon includes the extension of long-distance trade and the spread of material culture (including pottery), architectural elements and administrative devices from southern Iraq across Mesopotamia. Nevertheless, the reasons for the spread of this material culture are a major point of contention in archaeological debate. Within this paper, we apply a combined quantitative and qualitative methods featuring macroscopic observations, ceramic petrography and pXRF to a selection of 38 pottery sherds from Gurga Chiya, a small site located within the Shahrizor Plain, Iraqi Kurdistan. Results demonstrate that the pottery analysed was all locally produced, perhaps at Gurga Chiya itself. Potential reasons for the transmission of the Uruk Phenomenon and its appearance at Gurga Chiya are discussed. We suggest that frequent, low-level contacts between Gurga Chiya and communities of the Shahrizor and adjacent regions as a prospective reason for the transmission of this cultural package into the region

γ-Linolenic acid increases expression of key regulators of lipid metabolism in human skeletal muscle cells

Control of skeletal muscle fat metabolism is regulated acutely through Peroxisome Proliferator Activated Receptor (PPAR) δ activation and its downstream intracellular targets. The purpose of this study was to determine whether fatty acids with high binding affinity for PPARδ can elevate the expression of genes related to fatty acid oxidation and indicators of mitochondrial biogenesis in cultured human skeletal myotubes. Myotubes were treated for 72 hours with one of four conditions: (i) Control (CON); (ii) Eicosapentaenoic acid (EPA 250μM); (iii) γ-linolenic acid (γ-LA 250μM); (iv) PPARδ Agonist (GW501516 10nM). Incubation with γ-LA induced increases in the gene expression of CD36 (p= 0.005), HADHA (p= 0.022) and PDK4 (p=0.025) in comparison with CON, with no further differences observed between conditions. Furthermore, intensity of MitoTracker® Red immunostaining in myotubes increased following incubation with γ-LA (p≤ 0.001) and EPA (p= 0.005) however these trends were not mirrored in the expression of PGC-1α as might be expected. Overall, γ-LA elevates levels the transcription of key intracellular regulators of lipid metabolism and transport in human myotubes, which may be clinically beneficial in the control of metabolic diseases

In vitro 3D tissue modelling: Insights into ameloblastoma pathogenesis

Ameloblastoma is a rare, benign oral tumour. Tumours develop within the jaw bone and are highly destructive and invasive, with cells migrating into the jaw and surrounding soft tissue. This is a little-understood disease which if left untreated causes dramatic bone destruction and maxillofacial disfigurement. Current treatment is radical surgery, often resulting in extensive loss of function and tissue. An ameloblastoma-derived cell line, AM-1, has been established [1]. Cells were isolated from a human tumour and immortalised by the addition of HPV-16 DNA. This study aims to (i) make a 3D in vitro ameloblastoma disease model, using plastic-compressed collagen gel [2] seeded with AM-1 cells, and (ii) use this bone construct to characterise tissue remodelling, cell growth and invasiveness

Collagen gel as a 3D in vitro tissue model for ameloblastoma studies

Ameloblastoma is a rare locally invasive epithelial odontogenic tumour of the jaw which can cause significant and debilitating bone destruction. In vitro studies of ameloblastoma are sparse in the literature, and little is known regarding patterns of ameloblastoma cell growth and invasion, as well as relevant gene and protein expression. This study aims to (i) use plastic-compressed collagen gels as a robust and relevant biomimetic to culture ameloblastoma cells in a 3D in vitro tissue model [1] and (ii) perform histology, immunohistochemistry (IHC) and gene expression assays to characterise tissue remodelling, cell growth and invasiveness

Inferring Population Preferences via Mixtures of Spatial Voting Models

Understanding political phenomena requires measuring the political preferences of society. We introduce a model based on mixtures of spatial voting models that infers the underlying distribution of political preferences of voters with only voting records of the population and political positions of candidates in an election. Beyond offering a cost-effective alternative to surveys, this method projects the political preferences of voters and candidates into a shared latent preference space. This projection allows us to directly compare the preferences of the two groups, which is desirable for political science but difficult with traditional survey methods. After validating the aggregated-level inferences of this model against results of related work and on simple prediction tasks, we apply the model to better understand the phenomenon of political polarization in the Texas, New York, and Ohio electorates. Taken at face value, inferences drawn from our model indicate that the electorates in these states may be less bimodal than the distribution of candidates, but that the electorates are comparatively more extreme in their variance. We conclude with a discussion of limitations of our method and potential future directions for research.Comment: To be published in the 8th International Conference on Social Informatics (SocInfo) 201

Oral Mucosa Tissue Equivalents for the Treatment of Limbal Stem Cell Deficiency

Cultured limbal and oral epithelial cells have been successfully used to treat patients with limbal stem cell deficiency (LSCD). The most common culture method for these cell therapies utilizes amniotic membrane as a cell support and/or murine 3T3s as feeder fibroblasts. The aim of this study is to refine the production of autologous oral mucosal cell therapy for the treatment of LSCD. Real architecture for 3D tissue (RAFT) is used as an alternative cell culture support. In addition, oral mucosal cells (epithelial and fibroblast) are used as autologous alternatives to donor human limbal epithelial cells (HLE) and murine 3T3s. The following tissue equivalents are produced and characterized: first, for patients with bilateral LSCD, an oral mucosa tissue equivalent consisting of human oral mucosal epithelial cells on RAFT supported by human oral mucosal fibroblasts (HOMF). Second, for patients with unilateral LSCD, HLE on RAFT supported by HOMF. For both tissue equivalent types, features of the cornea are observed including a multi-layered epithelium with small cells with a stem cell like phenotype in the basal layer and squamous cells in the top layers, and p63α and PAX6 expression. These tissue equivalents may therefore be useful in the treatment of LSCD

Novel scaffolds for tissue engineering of human skeletal muscles

Tissue engineering is a multidisciplinary approach aimed at producing new organs and tissues for implantation in order to circumvent the limitations imposed by current techniques such as surgical tissue transfer. Structure begets function and highly ordered skeletal muscle (SkM) consists of elongated, multinucleate muscle cells (fibres) that are arranged in bundles surrounded by connective tissue sheaths. It is therefore of no surprise that tissue engineered SkM complexes are often designed around fibre containing scaffolds. This work is the natural continuation of strategies introduced at TCES 200

Comparison between Suitable Priors for Additive Bayesian Networks

Additive Bayesian networks are types of graphical models that extend the usual Bayesian generalized linear model to multiple dependent variables through the factorisation of the joint probability distribution of the underlying variables. When fitting an ABN model, the choice of the prior of the parameters is of crucial importance. If an inadequate prior - like a too weakly informative one - is used, data separation and data sparsity lead to issues in the model selection process. In this work a simulation study between two weakly and a strongly informative priors is presented. As weakly informative prior we use a zero mean Gaussian prior with a large variance, currently implemented in the R-package abn. The second prior belongs to the Student's t-distribution, specifically designed for logistic regressions and, finally, the strongly informative prior is again Gaussian with mean equal to true parameter value and a small variance. We compare the impact of these priors on the accuracy of the learned additive Bayesian network in function of different parameters. We create a simulation study to illustrate Lindley's paradox based on the prior choice. We then conclude by highlighting the good performance of the informative Student's t-prior and the limited impact of the Lindley's paradox. Finally, suggestions for further developments are provided.Comment: 8 pages, 4 figure

Neural and Aneural Regions Generated by the Use of Chemical Surface Coatings

The disordered environment found in conventional neural cultures impedes various applications where cell directionality is a key process for functionality. Neurons are highly specialized cells known to be greatly dependent on interactions with their surroundings. Therefore, when chemical cues are incorporated on the surface material, a precise control over neuronal behavior can be achieved. Here, the behavior of SH-SY5Y neurons on a variety of self-assembled monolayers (SAMs) and polymer brushes both in isolation and combination to promote cellular spatial control was determined. APTES and BIBB coatings promoted the highest cell viability, proliferation, metabolic activity, and neuronal maturation, while low cell survival was seen on PKSPMA and PMETAC surfaces. These cell-attractive and repulsive surfaces were combined to generate a binary BIBB-PKSPMA coating, whereby cellular growth was restricted to an exclusive neural region. The utility of these coatings when precisely combined could act as a bioactive/bioinert surface resulting in a biomimetic environment where control over neuronal growth and directionality can be achieved

Testosterone enables growth and hypertrophy in fusion impaired myoblasts that display myotube atrophy: deciphering the role of androgen and IGF-I receptors

We have previously highlighted the ability of testosterone to improve differentiation and myotube hypertrophy in fusion impaired myoblasts that display reduced myotube hypertrophy at 72hrs (after transfer to low serum media) via multiple population doublings (PD) vs. their parental controls (CON); an observation which is abrogated via PI3K/Akt inhibition (Deane et al. 2013). However, whether the most predominant molecular mechanism responsible for T induced hypertrophy occurs directly via androgen receptor or indirectly via IGF-IR/PI3K/Akt pathway is currently debated. PD and CON C2C12 muscle cells were exposed to low serum conditions in the presence or absence of T (100 nM) ± inhibitors of AR (flutamide/F, 40 μm) and IGF-IR (Picropodophyllin/PPP, 150 nM) for 72 hrs and 7 days (early/late muscle differentiation respectively). T increased AR and Akt abundance, myogenin expression, and myotube hypertrophy, but not ERK1/2 activity in both CON and PD cell types. Akt activity was not increased significantly in either cell type with T. Testosterone was unable to promote early differentiation in the presence of IGF-IR inhibitor (PPP) yet still able to promote appropriate later increases in myotube hypertrophy and AR abundance despite IGF-IR inhibition. The addition of the AR inhibitor powerfully attenuated all T induced increases in differentiation and myotube hypertrophy with corresponding reductions in AR abundance, phosphorylated Akt, ERK1/2 and gene expression of IGF-I, myoD and myogenin with increases in myostatin mRNA both cell types. Interestingly, despite basally reduced differentiation and myotube hypertrophy, PD cells showed larger increased in AR abundance vs. CON cells, a response abrogated in the presence of AR but not IGF-IR inhibitors. Furthermore, T induced increases in Akt abundance were sustained despite the presence of IGF-IR inhibition in PD cells only. However, flutamide alone reduced IGF-IR mRNA in both cell types across time points, with an observed reduction in activity of ERK and Akt, perhaps suggesting that IGF-IR was transcriptionally regulated by AR. However, where testosterone increased AR protein content there was no increases observed in IGF-IR gene expression. Overall, this suggested that sufficient AR was important to enable normal gene expression of IGF-IR and downstream signalling, yet elevated levels of AR due to testosterone had no further effect on IGF-IR, despite testosterone increasing Akt abundance in the presence of IGF-IR inhibitor. In conclusion, testosterones ability to improve differentiation and myotube hypertrophy occurred predominately via increases in AR and Akt abundance in both CON and PD cells, with fusion impaired cells (PD) showing an increased responsiveness to T induced AR levels. Finally, T induced increases in myotube hypertrophy (but not early differentiation) occurred independently of upstream IGF-IR input, however it appears that normal AR function in basal conditions is required for adequate IGF-IR gene expression and downstream Akt abundance