The Acquarossa Memory Project. Reconstructing an Etruscan town

Digital techniques and cultural heritage connect, in an innovative way, new and old within the Humanities. In this new project, an Etruscan townscape will be recreated; modelled results created by the 4D Research Lab will be integrated in an Archaeological Park and Museum in such a way that international scholars and visitors can acknowledge and study 3D reconstructions of a series of Etruscan houses within their successive phases of creation, function, reception, destruction, and reconstruction. Acquarossa is an Etruscan town near Viterbo, Italy. Excavations carried out by the Swedish Institute in Rome revealed a series of Etruscan houses, inhabited from the 8th century BC until the middle of the 6th century BC, when the town was suddenly and inexplicably abandoned. The houses were left to crumble and the remains of the foundations, the walls and the decorated roofs, as well as the thousands of household utensils, were all found in situ. It is one of the very few examples of an intact Etruscan townscape, with a unique set of family dwellings from the past. The remnants of the houses were partially reconstructed in the 1980s and covered with soil, but others were left to be destroyed by weather conditions. The site was left to vanish completely. Since 2014, the 4D Research Lab of the Faculty of Humanities of the University of Amsterdam has been involved in an interdisciplinary research project, in collaboration with the private partner Azienda Agrituristica Raffaele Rocchi, the proprietor of the site, which focuses on the reconstruction of a set of houses in annotated 3D models. The 3D models will be used to build ‘actual’ guesthouses at the site itself, for which permission from the Soprintendenza per i Beni archeologici del Lazio e dell’Etruria Meridionale has been granted. The project aims to analyse the house architecture, roof decoration and building processes through 3D modelling and scanning

Functional and structural deficits at accumbens synapses in a mouse model of Fragile X

International audienceFragile X is the most common cause of inherited intellectual disability and a leading cause of autism. The disease is caused by mutation of a single X-linked gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP), a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X patients suffer from cognitive and emotional deficits that coincide with abnormalities in dendritic spines. Changes in spine morphology are often associated with altered excitatory transmission and long-term plasticity, the most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of the mesocortico-limbic reward pathway, is now considered as a core structure in the control of social behaviors. Although the socio-affective impairments observed in Fragile X suggest dysfunctions in the accumbens, the impact of the lack of FMRP on accumbal synapses has scarcely been studied. Here we report for the first time a new spike timing-dependent plasticity paradigm that reliably triggers NMDAR-dependent long-term potentiation (LTP) of excitatory afferent inputs of medium spiny neurons (MSN) in the nucleus accumbens core region. Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant reduction of spontaneous NMDAR-mediated currents. In agreement with these physiological findings, we found significantly more filopodial spines in fmr1-/y mice by using an ultrastructural electron microscopic analysis of accumbens core medium spiny neuron spines. Surprisingly, spine elongation was specifically due to the longer longitudinal axis and larger area of spine necks, whereas spine head morphology and postsynaptic density size on spine heads remained unaffected in the fmr1-/y accumbens. These findings together reveal new structural and functional synaptic deficits in Fragile X

Measuring the Implementation and Effects of a Coordinated Care Model Featuring Diabetes Self-Management Education within Four Patient-Centered Medical Homes

Minority individuals experience a disproportionately greater incidence and prevalence of type 2 diabetes. Innovative approaches are needed to reduce health disparities and associated harms among vulnerable populations with diabetes. This thesis examines the effects of the implementation of a coordinated care model with underserved populations in Patient Centered Medical Homes (PCMH) at four sites (Florida, Ohio, Oklahoma, and Tennessee). The model featured diabetes self-management education (DSME) and a patient support intervention delivered within the PCMH context. The components of the comprehensive intervention included DSME, support for managing diabetes and distress, enhanced access and linkage to care, and improvement to quality of care. The primary dependent measures in this study included four clinical health measures—glycosylated hemoglobin (A1C), blood pressure, body mass index, and lipids—and the AADE7 Self-Care BehaviorsTM. Coordinated care teams that delivered the intervention included primary care physicians, nurse care coordinators, certified diabetes educators, health behavior coaches, and diabetes patient supporters. Community health workers and medical assistants provided additional individualized support to patients. Care teams provided DSME as well as customized and coordinated patient support within a PCMH setting. This study was part of a larger participatory evaluation of the Bristol-Myers Squibb Foundation’s Together on Diabetes initiative. A statistically significant decrease was seen in A1C, the primary clinical health outcome. This decrease was seen across all four implementation sites; ranging from a decrease of 0.4% to 0.9% after 6 months. This improved A1C level was associated with implementation of the DSME and support intervention. Substantial policy and practice changes were also brought about at two of the four PCMH sites. Use of DSME within the PCMH model is a promising strategy for reducing clinical markers for diabetes among vulnerable populations. Systems changes, including policy and practice changes, have the potential to have lasting effects within PCMH practice for reducing the burden of diabetes

Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome

Fragile X syndrome, the most commonly known genetic cause of autism, is due to loss of the fragile X mental retardation protein, which regulates signal transduction at metabotropic glutamate receptor-5 in the brain. Fragile X mental retardation protein deletion in mice enhances metabotropic glutamate receptor-5-dependent long-term depression in the hippocampus and cerebellum. Here we show that a distinct type of metabotropic glutamate receptor-5-dependent long-term depression at excitatory synapses of the ventral striatum and prefrontal cortex, which is mediated by the endocannabinoid 2-arachidonoyl-sn-glycerol, is absent in fragile X mental retardation protein-null mice. In these mutants, the macromolecular complex that links metabotropic glutamate receptor-5 to the 2-arachidonoyl-sn-glycerolproducing enzyme, diacylglycerol lipase-α (endocannabinoid signalosome), is disrupted and metabotropic glutamate receptor-5-dependent 2-arachidonoyl-sn-glycerol formation is compromised. These changes are accompanied by impaired endocannabinoid-dependent long-term depression. Pharmacological enhancement of 2-arachidonoyl-sn-glycerol signalling normalizes this synaptic defect and corrects behavioural abnormalities in fragile X mental retardation protein-deficient mice. The results identify the endocannabinoid signalosome as

Systemic coagulopathy promotes host lethality in a new Drosophila tumor model.

Malignant tumors trigger a complex network of inflammatory and wound repair responses, prompting Dvoraks characterization of tumors as wounds that never heal.1 Some of these responses lead to profound defects in blood clotting, such as disseminated intravascular coagulopathy (DIC), which correlate with poor prognoses.2,3,4 Here, we demonstrate that a new tumor model in Drosophila provokes phenotypes that resemble coagulopathies observed in patients. Fly ovarian tumors overproduce multiple secreted components of the clotting cascade and trigger hypercoagulation of fly blood (hemolymph). Hypercoagulation occurs shortly after tumor induction and is transient; it is followed by a hypocoagulative state that is defective in wound healing. Cellular clotting regulators accumulate on the tumor over time and are depleted from the body, suggesting that hypocoagulation is caused by exhaustion of host clotting components. We show that rescuing coagulopathy by depleting a tumor-produced clotting factor improves survival of tumor-bearing flies, despite the fact that flies have an open (non-vascular) circulatory system. As clinical studies suggest that lethality in patients with high serum levels of clotting components can be independent of thrombotic events,5,6 our work establishes a platform for identifying alternative mechanisms by which tumor-driven coagulopathy triggers early mortality. Moreover, it opens up exploration of other conserved mechanisms of host responses to chronic wounds