Planning for Institutional Development and Developing Budgets and Financial Management Systems

This section lays out issues related to strategic planning by the Foundation for Community Development (FDC) and illustrates the development of budgets and financial management systems by the Philippine Business for Social Progress (PBSP). Also explored here is the financial reporting system set up by the Esquel Ecuador Foundation (FEE) for their grantees

Outcomes in Living Liver Donor “Heroes” After the Spotlight Fades

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149256/1/lt25459_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149256/2/lt25459.pd

Reply

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156149/2/lt25763.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156149/1/lt25763_am.pd

Recommended terminology concerning people with a criminal conviction

This guide to terminology has been created to support staff and students in understanding helpful and appropriate ways to refer to people who have previously been convicted of a criminal offence. It has been put together with input from a survey of NTU Psychology staff, best practice guidance from the American Psychological Association, The Marshall (Language) Project, Her Majesty’s Prison and Probation Service, academic journals, research, and individuals with a vested interest in the use of language that supports rather than excludes

Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure

Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70) from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further, the robust change in non-synaptic proteins suggests that AIE may prime this signaling pathway for future ethanol exposures in adulthood

Gender Disparities in Alcohol Use Disorder Treatment Among Privately Insured Patients with Alcohol‐Associated Cirrhosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147837/1/acer13944_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147837/2/acer13944.pd

Development of a Large-Scale Integrated Neurocognitive Architecture Part 1: Conceptual Framework

The idea of creating a general purpose machine intelligence that captures many of the features of human cognition goes back at least to the earliest days of artificial intelligence and neural computation. In spite of more than a half-century of research on this issue, there is currently no existing approach to machine intelligence that comes close to providing a powerful, general-purpose human-level intelligence. However, substantial progress made during recent years in neural computation, high performance computing, neuroscience and cognitive science suggests that a renewed effort to produce a general purpose and adaptive machine intelligence is timely, likely to yield qualitatively more powerful approaches to machine intelligence than those currently existing, and certain to lead to substantial progress in cognitive science, AI and neural computation. In this report, we outline a conceptual framework for the long-term development of a large-scale machine intelligence that is based on the modular organization, dynamics and plasticity of the human brain. Some basic design principles are presented along with a review of some of the relevant existing knowledge about the neurobiological basis of cognition. Three intermediate-scale prototypes for parts of a larger system are successfully implemented, providing support for the effectiveness of several of the principles in our framework. We conclude that a human-competitive neuromorphic system for machine intelligence is a viable long- term goal, but that for the short term, substantial integration with more standard symbolic methods as well as substantial research will be needed to make this goal achievable

Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153137/1/lt25681.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153137/2/lt25681_am.pd

Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation

AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. This has led to considerable interest in AMPK as a therapeutic target for the metabolic dysfunction observed in obesity and insulin resistance. The role of AMPK in skeletal muscle and the liver has been extensively studied, such that AMPK has been demonstrated to inhibit synthesis of fatty acids, cholesterol and isoprenoids, hepatic gluconeogenesis and translation while increasing fatty acid oxidation, muscle glucose transport, mitochondrial biogenesis and caloric intake. The role of AMPK in the other principal metabolic and insulin-sensitive tissue, adipose, remains poorly characterized in comparison, yet increasing evidence supports an important role for AMPK in adipose tissue function. Obesity is characterized by hypertrophy of adipocytes and the development of a chronic sub-clinical pro-inflammatory environment in adipose tissue, leading to increased infiltration of immune cells. This combination of dysfunctional hypertrophic adipocytes and a pro-inflammatory environment contributes to insulin resistance and the development of Type 2 diabetes. Exciting recent studies indicate that AMPK may not only influence metabolism in adipocytes, but also act to suppress this pro-inflammatory environment, such that targeting AMPK in adipose tissue may be desirable to normalize adipose dysfunction and inflammation. In the present review, we discuss the role of AMPK in adipose tissue, focussing on the regulation of carbohydrate and lipid metabolism, adipogenesis and pro-inflammatory pathways in physiological and pathophysiological conditions

Thermodynamic stability, unfolding kinetics, and aggregation of the N-terminal actin-binding domains of utrophin and dystrophin.

Muscular dystrophy (MD) is the most common genetic lethal disorder in children. Mutations in dystrophin trigger the most common form of MD, Duchenne, and its allelic variant Becker MD. Utrophin is the closest homologue and has been shown to compensate for the loss of dystrophin in human disease animal models. However, the structural and functional similarities and differences between utrophin and dystrophin are less understood. Both proteins interact with actin through their N-terminal actin-binding domain (N-ABD). In this study, we examined the thermodynamic stability and aggregation of utrophin N-ABD and compared with that of dystrophin. Our results show that utrophin N-ABD has spectroscopic properties similar to dystrophin N-ABD. However, utrophin N-ABD has decreased denaturant and thermal stability, unfolds faster, and is correspondingly more susceptible to proteolysis, which might account for its decreased in vivo half-life compared to dystrophin. In addition, utrophin N-ABD aggregates to a lesser extent compared with dystrophin N-ABD, contrary to the general behavior of proteins in which decreased stability enhances protein aggregation. Despite these differences in stability and aggregation, both proteins exhibit deleterious effects of mutations. When utrophin N-ABD mutations analogous in position to the dystrophin disease-causing mutations were generated, they behaved similarly to dystrophin mutants in terms of decreased stability and the formation of cross-β aggregates, indicating a possible role for utrophin mutations in disease mechanisms