In vivo Dopamine Efflux is Decreased in Striatum of both Fragment (R6/2) and Full-Length (YAC128) Transgenic Mouse Models of Huntington's Disease

Huntington's disease (HD) is characterized by numerous alterations within the corticostriatal circuitry. The striatum is innervated by a dense array of dopaminergic (DA) terminals and these DA synapses are critical to the proper execution of motor functions. As motor disturbances are prevalent in HD we examined DA neurotransmission in the striatum in transgenic (tg) murine models of HD. We used in vivo microdialysis to compare extracellular concentrations of striatal DA in both a fragment (R6/2) model, which displays a rapid and severe phenotype, and a full-length (YAC128) model that expresses a more progressive phenotype. Extracellular striatal DA concentrations were significantly reduced in R6/2 mice and decreased concomitantly with age-dependent increasing motor impairments on the rotarod task (7, 9, and 11 weeks). In a sample of 11-week-old R6/2 mice, we also measured tissue concentrations of striatal DA and found that total levels of DA were significantly depleted. However, the loss of total DA content (<50%) was insufficient to account for the full extent of DA depletion in the extracellular fluid (ECF; ∼75%). We also observed a significant reduction in extracellular DA concentrations in the striatum of 7-month-old YAC128 mice. In a separate set of experiments, we applied d-amphetamine (AMPH; 10 μm) locally into the striatum to stimulate the release of intracellular DA into the ECF. The AMPH-induced increase in extracellular DA levels was significantly blunted in 9-week-old R6/2 mice. There also was a decrease in AMPH-stimulated DA efflux in 7-month-old YAC128 mice in comparison to WT controls, although the effect was milder. In the same cohort of 7-month-old YAC128 mice we observed a significant reduction in the total locomotor activity in response to systemic AMPH (2 mg/kg). Our data demonstrate that extracellular DA release is attenuated in both a fragment and full-length tg mouse model of HD and support the concept of DA involvement in aspects of the syndrome

Molecular analyses of confiscated shark fins reveal shortcomings of CITES implementations in Germany

A three-ton shipment of dry shark fins was examined by German customs in 2017 leading to the confiscation of 405 kg of potential CITES species. We analyzed a subsample of this material (115 specimens) using DNA sequence-based identification and compared results to morphological screening of CITES species. We found a mixture of CITES regulated (4 of 11 species) and unregulated shark species. Our results demonstrate the difficulties of identifying CITES species morphologically in large fin shipments of mixed species composition. Correct identification of CITES species based on morphology alone may be hindered by missing characters or those altered by drying. We therefore suggest random molecular screening as a uniform approach for German customs authorities to check species composition and identify CITES regulated species in transit shipments.publishedVersio

Religion as a Chinese Cultural Component: Culture in the Chinese Taoist Association and Confucius Institute

This thesis examines the role of the cultural discourse on the indigenous religious traditions of China and their place within an officially sanctioned construction of Chinese culture. It starts by examining the concept of culture as it developed in the modern era, its place within the construction of national identities, and the marginalizing effects this has on certain members of national populations. Next it turns to the development of the cultural discourse within China from the mid-1800s to the Cultural Revolution, highlighting the social and legal transformations as they restricted and reframed the practice and articulation of religious traditions in mainland China. Following these early articulations of a cultural discourse in China and the subjugation of religious traditions to secular standards of legitimation, it examines the official presentations and governmentally sanctioned forms of the Daoist tradition in post-Mao China during a “cultural revival,” through an analysis of official publications and online presentations. Finally, it examines the way teachers and administrators package Chinese culture for a foreign audience through the Confucius Institute. This thesis argues that, despite greater freedom to explore indigenous traditions previously written off as “superstitious” within the cultural revival of contemporary China, the official cultural discourse in China continues to operate within the parameters of a modern cultural identity that marginalizes ritualistic forms of religion, allowing these religious forms to survive in an official space only as exotic images, sanitized and secularized activities, or ethical ideals

Collective and single cell behavior in epithelial contact inhibition

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition". The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured MDCK cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition

Rhythm and Vowel Quality in Accents of English

In a sample of 27 speakers of Scottish Standard English two notoriously variable consonantal features are investigated: the contrast of /m/ and /w/ and non-prevocalic /r/, the latter both in terms of its presence or absence and the phonetic form it takes, if present. The pattern of realisation of non-prevocalic /r/ largely confirms previously reported findings. But there are a number of surprising results regarding the merger of /m/ and /w/ and the loss of non-prevocalic /r/: While the former is more likely to happen in younger speakers and females, the latter seems more likely in older speakers and males. This is suggestive of change in progress leading to a loss of the /m/ - /w/ contrast, while the variation found in non-prevocalic /r/ follows an almost inverse sociolinguistic pattern that does not suggest any such change and is additionally largely explicable in language-internal terms. One phenomenon requiring further investigation is the curious effect direct contact with Southern English accents seems to have on non-prevocalic /r/: innovation on the structural level (i.e. loss) and conservatism on the realisational level (i.e. increased incidence of [r] and [r]) appear to be conditioned by the same sociolinguistic factors

Physiological Release of Striatal Acetylcholine In Vivo: Modulation by Dl and D2 Dopamine Receptor Subtypes1

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Distribution of Tyrosine Hydroxylase-Expressing Interneurons with Respect to Anatomical Organization of the Neostriatum

We have recently shown in vitro that striatal tyrosine hydroxylase-expressing interneurons identified in transgenic mice by expression of enhanced green fluorescent protein (TH-eGFP) display electrophysiological profiles that are distinct from those of other striatal interneurons. Furthermore, striatal TH-eGFP interneurons show marked diversity in their electrophysiological properties and have been divided into four distinct subtypes. One question that arises from these observations is whether striatal TH-eGFP interneurons are distributed randomly, or obey some sort of organizational plan as has been shown to be the case with other striatal interneurons. An understanding of the striatal TH-eGFP interneuronal patterning is a vital step in understanding the role of these neurons in striatal functioning. Therefore, in the present set of studies the location of electrophysiologically identified striatal TH-eGFP interneurons was mapped. In addition, the distribution of TH-eGFP interneurons with respect to the striatal striosome–matrix compartmental organization was determined using μ-opioid receptor (MOR) immunofluorescence or intrinsic TH-eGFP fluorescence to delineate striosome and matrix compartments. Overall, the distribution of the different TH-eGFP interneuronal subtypes did not differ in dorsal versus ventral striatum. However, striatal TH-eGFP interneurons were found to be mostly in the matrix in the dorsal striatum whereas a significantly higher proportion of these neurons was located in MOR-enriched domains of the ventral striatum. Further, the majority of striatal TH-eGFP interneurons was found to be located within 100 μm of a striosome–matrix boundary. Taken together, the current results suggest that TH-eGFP interneurons obey different organizational principles in dorsal versus ventral striatum, and may play a role in communication between striatal striosome and matrix compartments

Pleasure and pedagogy: the consumption of DVD add-ons among Irish teenagers

This article addresses the issue of young people and media use in the digital age, more specifically the interconnection between new media pleasures and pedagogy as they relate to the consumption of DVD add-ons. Arguing against the view of new media as having predominantly detrimental effects on young people, the authors claim that new media can enable young people to develop media literacy skills and are of the view that media literacy strategies must be based on an understanding and legitimating of young people's use patterns and pleasures. The discussion is based on a pilot research project on the use patterns and pleasures of use with a sample of Irish teenagers. They found that DVDs were used predominantly in the home context, and that, while there was variability in use between the groups, overall they developed critical literacy skills and competences which were interwoven into their social life and projects of identity construction. The authors suggest that these findings could be used to develop DVDs and their add-on features as a learning resource in the more formal educational setting and they go on to outline the potential teaching benefits of their use across a range of pedagogical areas

Managing for change: October 11, 1989

Bi-weekly newsletter of University Hospital's Change Project, provided to managers at the hospital

Orbital inflammatory complications of Crohn’s disease: a rare case series

Orbital inflammatory disease is a rare ophthalmic manifestation of Crohn’s disease. Inflammation is characteristically non-specific, involving one or multiple structures of the orbit. Mechanisms of disease and optimal methods of treatment are poorly understood. The aim of this report is to present three cases of orbital involvement in Crohn’s disease. A retrospective case note review of patients with orbital inflammatory disease and Crohn’s disease was performed at our academic centre to determine the clinical, imaging and histopathological features of this condition and its relationship to intestinal Crohn’s disease. Three patients were identified with orbital inflammatory manifestations complicating Crohn’s disease. All patients described were female with active intestinal disease and had a history of treatment with immunosuppressive therapies. Similarities were observed in clinical presentations with variance noted in radiological and histopathological findings. In all cases, symptoms improved with oral corticosteroids or non-steroidal drugs in combination with anti-tumour necrosis factor (anti-TNF) agents. Inflammatory bowel disease-related orbital complications are rare but potentially vision-threatening. It is important to consider mimics of orbital inflammatory disease such as systemic inflammatory disease, malignancy, congenital malformations, infection and trauma when formulating a comprehensive differential diagnosis. Therapeutic intervention is directed towards preservation of vision and orbital function and reducing the acute inflammatory process. Corticosteroids are typically the initial treatment of choice for moderate-to-severe disease, although several classes of immunomodulatory agents have been variably useful in treating this condition. Heightened awareness and close cooperation between gastroenterologists and ophthalmologists is mandatory