To investigate the physiological role of arcuate nucleus cocaine- and amphetamine- regulated transcript in energy homeostasis

Cocaine- and amphetamine- regulated transcript (CART) was originally identified as a mRNA transcript upregulated in rats in response to administration of cocaine and amphetamine. CART is widely expressed in the central nervous system (CNS) with high levels of expression in hypothalamic nuclei such as the arcuate nucleus (ARC). CART was initially thought to act as an anorectic peptide since it is coexpressed with the anorectic neuropeptide pro-opiomelanocortin (POMC) in the ARC. In addition, intracerebroventricular (ICV) administration of CART (55-102) peptide inhibits feeding and administration of anti-CART antibody results in stimulation of feeding. However, subsequent studies have suggested CART may also act as an orexigen since injection of CART (55-102) specifically into the ARC and ventromedial nucleus (VMN) of the hypothalamus results in a significant increase in food intake. These data suggest CART acts through both anorectic and orexigenic circuits. Given the importance of the hypothalamus in the regulation of energy homeostasis, and the role of the ARC in integrating peripheral signals, it is essential to elucidate the role of ARC derived CART. In order to elucidate CART’s true physiological role in the ARC I used a combination of genetic approaches. I generated a recombinant Adeno-associated virus (rAAV) expressing CART antisense (CART-AS) and a transgenic mouse model which utilises the POMC promoter to drive expression of CART-AS. In the transgenic CART-AS model mice exhibited a significantly higher body weight relative to control animals, no significant difference in food intake was observed. In addition, mice expressing the CART-AS transgene demonstrated a reduction in uncoupling protein-1 (UCP- 1) mRNA expression in brown adipose tissue (BAT) which is suggestive of decreased thermogenesis. This may explain the observed increase in body weight in the transgenic mice. Bilateral intra-ARC injections of rAAV-CART-AS resulted in a significant increase in cumulative food intake and body weight gain compared to control animals. There was no significant difference in activity or metabolism levels. The data presented in my thesis provides an important contribution to understanding the role of CART within the ARC. The results from my genetic studies appear to suggest that ARC derived CART has an anorectic role

Tackling Africa's chronic disease burden: from the local to the global.

Africa faces a double burden of infectious and chronic diseases. While infectious diseases still account for at least 69% of deaths on the continent, age specific mortality rates from chronic diseases as a whole are actually higher in sub Saharan Africa than in virtually all other regions of the world, in both men and women. Over the next ten years the continent is projected to experience the largest increase in death rates from cardiovascular disease, cancer, respiratory disease and diabetes. African health systems are weak and national investments in healthcare training and service delivery continue to prioritise infectious and parasitic diseases. There is a strong consensus that Africa faces significant challenges in chronic disease research, practice and policy. This editorial reviews eight original papers submitted to a Globalization and Health special issue themed: "Africa's chronic disease burden: local and global perspectives". The papers offer new empirical evidence and comprehensive reviews on diabetes in Tanzania, sickle cell disease in Nigeria, chronic mental illness in rural Ghana, HIV/AIDS care-giving among children in Kenya and chronic disease interventions in Ghana and Cameroon. Regional and international reviews are offered on cardiovascular risk in Africa, comorbidity between infectious and chronic diseases and cardiovascular disease, diabetes and established risk factors among populations of sub-Saharan African descent in Europe. We discuss insights from these papers within the contexts of medical, psychological, community and policy dimensions of chronic disease. There is an urgent need for primary and secondary interventions and for African health policymakers and governments to prioritise the development and implementation of chronic disease policies. Two gaps need critical attention. The first gap concerns the need for multidisciplinary models of research to properly inform the design of interventions. The second gap concerns understanding the processes and political economies of policy making in sub Saharan Africa. The economic impact of chronic diseases for families, health systems and governments and the relationships between national policy making and international economic and political pressures have a huge impact on the risk of chronic diseases and the ability of countries to respond to them.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Enhanced automatic action imitation and intact imitation- inhibition in schizophrenia

Imitation plays a key role in social learning and in facilitating social interactions and likely constitutes a basic building block of social cognition that supports higher-level social abilities. Recent findings suggest that patients with schizophrenia have imitation impairments that could contribute to the social impairments associated with the disorder. However, extant studies have specifically assessed voluntary imitation or automatic imitation of emotional stimuli without controlling for potential confounders. The imitation impairments seen might therefore be secondary to other cognitive, motoric or emotional deficits associated with the disorder. To overcome this issue, we used an automatic imitation paradigm with nonemotional stimuli to assess automatic imitation and the top-down modulation of imitation where participants were required to lift one of two fingers according to a number shown on the screen whilst observing the same or the other finger movement. In addition, we used a control task with a visual cue in place of a moving finger, to isolate the effect of observing finger movement from other visual cueing effects. Data from 33 patients (31 medicated) and 40 matched healthy controls were analyzed. Patients displayed enhanced imitation and intact top-down modulation of imitation. The enhanced imitation seen in patients may have been medication induced as larger effects were seen in patients receiving higher antipsychotic doses. In sum, we did not find an imitation impairment in schizophrenia. The results suggest that previous findings of impaired imitation in schizophrenia might have been due to other cognitive, motoric and/or emotional deficits

The future of human nature: a symposium on the promises and challenges of the revolutions in genomics and computer science, April 10, 11, and 12, 2003

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's Symposium on the Promises and Challenges of the Revolutions in Genomics and Computer Science took place during April 10, 11, and 12, 2003. Co-organized by Charles DeLisi and Kenneth Lewes; sponsored by Boston University, the Frederick S. Pardee Center for the Study of the Longer-Range Future.This conference focused on scientific and technological advances in genetics, computer science, and their convergence during the next 35 to 250 years. In particular, it focused on directed evolution, the futures it allows, the shape of society in those futures, and the robustness of human nature against technological change at the level of individuals, groups, and societies. It is taken as a premise that biotechnology and computer science will mature and will reinforce one another. During the period of interest, human cloning, germ-line genetic engineering, and an array of reproductive technologies will become feasible and safe. Early in this period, we can reasonably expect the processing power of a laptop computer to exceed the collective processing power of every human brain on the planet; later in the period human/machine interfaces will begin to emerge. Whether such technologies will take hold is not known. But if they do, human evolution is likely to proceed at a greatly accelerated rate; human nature as we know it may change markedly, if it does not disappear altogether, and new intelligent species may well be created

The future of human nature: a symposium on the promises and challenges of the revolutions in genomics and computer science, April 10, 11, and 12, 2003

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's Symposium on the Promises and Challenges of the Revolutions in Genomics and Computer Science took place during April 10, 11, and 12, 2003. Co-organized by Charles DeLisi and Kenneth Lewes; sponsored by Boston University, the Frederick S. Pardee Center for the Study of the Longer-Range Future.This conference focused on scientific and technological advances in genetics, computer science, and their convergence during the next 35 to 250 years. In particular, it focused on directed evolution, the futures it allows, the shape of society in those futures, and the robustness of human nature against technological change at the level of individuals, groups, and societies. It is taken as a premise that biotechnology and computer science will mature and will reinforce one another. During the period of interest, human cloning, germ-line genetic engineering, and an array of reproductive technologies will become feasible and safe. Early in this period, we can reasonably expect the processing power of a laptop computer to exceed the collective processing power of every human brain on the planet; later in the period human/machine interfaces will begin to emerge. Whether such technologies will take hold is not known. But if they do, human evolution is likely to proceed at a greatly accelerated rate; human nature as we know it may change markedly, if it does not disappear altogether, and new intelligent species may well be created

Agricultural producer perceptions of climate change and climate education needs for the Central Great Plains

Citation: Hibbs, Amber Campbell, Daniel Kahl, Lisa PytlikZillig, Ben Champion, Tarik Abdel-Monem, Timothy Steffensmeier, Charles W. Rice, and Kenneth Hubbard. “Agricultural Producer Perceptions of Climate Change and Climate Education Needs for the Central Great Plains.” Journal of Extension 52, no. 3 (June 2014). https://www.joe.org/joe/2014june/a2.php.The Central Great Plains Climate Education Partnership conducted focus groups throughout Kansas to gain a better understanding of farmer perceptions and attitudes towards climate change education. Results indicate concern about climatic changes, even if producers are unsure that "human caused climate change" is occurring. Participants indicated they would like access to information through Web-based programs that allow them to manipulate variables relevant to their area and situation. Participants prefer locally relevant information and identified Extension agents as trusted educators. The study provided an expanded understanding of agricultural producer perceptions that will be valuable to individuals or organizations providing climate education

Additional Evaluation of the Point-of-Contact Circulating Cathodic Antigen Assay for Schistosoma mansoni Infection.

Studies of the urine-based point-of-contact cathodic circulating antigen test (POC-CCA) in Schistosoma mansoni-endemic settings in Africa indicate it has good sensitivity in detecting infections, but in areas of low prevalence, the POC-CCA can be positive for persons who are egg-negative by Kato-Katz stool assays. We examined the POC-CCA assay for: (a) batch-to-batch stability; (b) intra-reader and inter-reader variability; (c) day-to-day variability compared to Kato-Katz stool assays, and (d) to see if praziquantel (PZQ) treatment converted Kato-Katz-negative/POC-CCA positive individuals to POC-CCA negativity. We found essentially no batch-to-batch variation, negligible intra-reader variability (2%), and substantial agreement for inter-reader reliability. Some day-to-day variation was observed over 5 days of urine collection, but less than the variation in Kato-Katz stool assays over 3 days. To evaluate the effect of treatment on Kato-Katz(-)/POC-CCA(+) children, 149 children in an area of 10-15% prevalence who were Kato-Katz(-) based on 3 stool samples but POC-CCA(+) were enrolled. Seven days after treatment (PZQ 40 mg/kg) samples were again collected and tested. Almost half (47%) POC-CCA positive children turned negative. Those still POC-CCA positive received a second treatment, and 34% of them turned POC-CCA negative upon this second treatment. Most who remained POC-CCA positive shifted each time to a "lesser" POC-CCA "level of positivity." The data suggest that most Kato-Katz-negative/POC-CCA positive individuals harbor low-intensity infections, and each treatment kills all or some of their adult worms. The data also suggest that when evaluated by a more sensitive assay, the effective cure rates for PZQ are significantly less than those inferred from fecal testing. These findings have public health significance for the mapping and monitoring of Schistosoma infections and in planning the transition from schistosomiasis morbidity control to elimination of transmission

IL-18 neutralization ameliorates obstruction-induced epithelial–mesenchymal transition and renal fibrosis

Ureteral obstruction results in renal fibrosis in part due to inflammatory injury. The role of interleukin-18 (IL-18), an important mediator of inflammation, in the genesis of renal fibrosis was studied using transgenic mice overexpressing human IL-18-binding protein. In addition, HK-2 cells were analyzed following direct exposure to IL-18 compared to control media. Two weeks after ureteral obstruction, the kidneys of wild-type mice had a significant increase in IL-18 production, collagen deposition, α-smooth muscle actin and RhoA expression, fibroblast and macrophage accumulation, chemokine expression, and transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) production, whereas E-cadherin expression was simultaneously decreased. The transgenic mice with neutralized IL-18 activity exhibited significant reductions in these indicators of obstruction-induced renal fibrosis and epithelial– mesenchymal transition, without demonstrating alterations in TGF-β1 or TNF-α activity. Similarly, the HK-2 cells exhibited increased α-smooth muscle actin expression and collagen production, and decreased E-cadherin expression in response to IL-18 stimulation without alterations in TNF-α or TGF-β1 activity. Our study demonstrates that IL-18 is a significant mediator of obstruction-induced renal fibrosis and epithelial– mesenchymal transition independent of downstream TGF-β1 or TNF-α production

Concert recording 2017-12-01

[Tracks 1-15]. 15 etudes op. 76(a) / David Popper -- [Track 16]. Suite no. 1, BWV 1007. Prelude [Track 17]. Sarabande [Track 18]. Minuet. / Johann Sebastian Bach -- [Track 19]. Suite no. 2, BWV 1008. Prelude [Track 20]. Gigue [Track 21]. Allemande [Track 22]. Courante [Track 23]. Sarabande [Track 24]. Minuet. / Johann Sebastian Bach -- [Track 25]. Suite no. 3, BWV 1009. Prelude [Track 26]. Allemande [Track 27]. Courante [Track 28]. Bourreé [Track 29]. Sarabande [Track 30]. Gigue / Johann Sebastian Bach -- [Track 31]. Suite no. 1, BWV 1007.Prelude [Track 32]. Courante [Track 33]. Sarabande / Johann Sebastian Bach -- [Track 34] Suite No. 4, BWV 1010. Prelude [Track 35]. Sarabande / Johann Sebastian Bach -- [Track 36]. Sicilienne / Maria Theresia von Paradis arranged by Dominic K Na -- [Track 37]. Ständchen / Franz Schubert arranged by Dominic K Na -- [Track 38]. The ragtime dance / Scott Joplin arranged by Dominic K Na