824 research outputs found
Public Media and Political Independence: Lessons for the Future of Journalism From Around the World
Profiles how fourteen nations fund and protect the autonomy of public media via multiyear funding, public-linked funding structures, charters, laws, and agencies or boards designed to limit political influence and ensure spending in the public interest
Energetic Consequences for a Northern, Range-Edge Lizard Population
Lizards at the northern, cool edge of their geographic range in the northern hemisphere should encounter environmental conditions that differ from those living near the core of their range. To better understand how modest climate differences affect lizard energetics, we compared daily feeding and metabolism rates of individual Sceloporus occidentalis in two populations during mid-summer. Chuckanut Beach (CB) was a cool, maritime climate in northern Washington State, and Sondino Ranch (SR) was a warmer, drier climate in southern, inland Washington. We found no difference between populations in daily energy expenditure (DEE), as calculated from doubly labeled water estimates. The CB population, however, had significantly higher prey availability and rate of daily energy intake (DEI) as estimated from fecal pellet masses. Consequently, CB lizards had higher size-adjusted body masses than lizards from SR. Within CB, during midsummer, DEE was similar to DEI. Within the SR population, DEE trended higher than DEI during midsummer, but was not significantly different. We found no population differences in lizard activity, active body temperature, or preferred body temperature. Hence, we infer the longer activity season for the SR population may compensate for the low food availability and high daily energy cost of midsummer. Moreover, for the CB population, we infer that cooler temperatures and higher food availability allow the lizards to compensate for the shorter activity. We also suggest the CB population may benefit from the predicted warmer temperatures associated with climate change given the similar activity-period body temperatures and DEE between these lizard populations assuming food availability is sufficient
Explaining The Appearance and Success of Voter Referenda For Open-Space Conservation
This paper provides an empirical investigation of the factors that in?uence the appearance and success of voter referenda for policies designed to promote open-space conservation. We take advantage of a data set that includes detailed information on all such referenda that occurred in the United States between 1998 and 2003. Combining these data with information from the U.S. Census, we conduct a nationwide analysis along with focused analyses of referenda that occurred in New Jersey and Massachusetts. Among the questions that we consider are the following: What factors contribute to the appearance of an open- space referendum in a jurisdiction? How does an initiative's funding mechanism, such as a bond, property tax, sales tax, or income tax, affect the way citizens vote? How responsive are favorable votes to the costs of an open-space initiative? And how do socioeconomic characteristics affect demand for public provision of open space?
Doctor of Philosophy
dissertationProgrammed cell death 4 (PDCD4) has been described as a tumor suppressor in multiple cancer cell types. In vitro, exogenous expression of PDCD4 results in decreased anchorage-independent cell growth and invasion. These anticancer phenotypes are attributed to inhibition of the translation initiation factor eIF4A when bound to PDCD4. In this dissertation, I report the discovery of novel interactions with the nuclear pore protein Nup153, the exon junction core protein eIF4AIII, and protein arginine methyltransferase 5 (PRMT5) that may modulate PDCD4 in a cancer context. PDCD4 levels are often suppressed in cancerous cells compared to normal surrounding tissues, and elevated expression in tumors is correlated with better survival outcomes. Despite this, 20-30% of patients with tumors that express high levels of PDCD4 have poor outcomes, indicating that these cancers deactivate PDCD4. Our analyses of transcript expression in breast cancer patients show that simultaneous upregulation of PRMT5 with PDCD4 results in poor survival outcomes. Using an orthotopic tumor model, I demonstrate that simultaneous expression of PDCD4 and PRMT5 in the breast cancer cell line MCF7 causes accelerated tumor growth. This tumor growth phenotype is dependent on PRMT5 enzymatic activity and the PDCD4 Nterminal site that is modified by PRMT5. This demonstrates that PDCD4 tumor suppressor function is radically altered when modified by PRMT5. Furthermore, this provides a mechanism for poor outcomes in patients with tumors that express elevated iv PDCD4. These findings show the utility of tracking both PDCD4 and PRMT5 as biomarkers and reveals PRMT5 as a potential target of chemotherapy. Finally, PDCD4 acts as a tumor suppressor through inhibition of the RNA helicase activity of eIF4A, although the precise mechanism of how this is accomplished has been unknown. In this dissertation, I report that PDCD4 interferes with the ability of eIF4A to interact with RNA, thereby deactivating its RNA helicase function. This provides a clear in vitro mechanism for eIF4A inhibition by PDCD4
Homeowner Association Standing in California: A Proposal to Expand the Role of the Unit Owner
Effects of stress, acute alcohol treatment, or both on pre-pulse inhibition in high- and low-alcohol preferring mice
Pre-pulse inhibition of the acoustic startle reflex (PPI) is a measure of sensorimotor gating frequently used to assess information processing in both humans and rodents. Both alcohol and stress exposure can modulate PPI, making it possible to assess how stress and alcohol interact to influence information processing. Humans with an increased genetic risk for alcoholism are more reactive to stressful situations compared to those without a family history, and alcohol may have stress-dampening effects for those with high genetic risk. The purpose of the present study was to examine the effects of stress, acute alcohol exposure, or both on PPI in male and female mice selectively bred for high- (HAP2) and low- (LAP2) alcohol preference. Experiment 1 assessed the effects of various doses of acute alcohol on PPI. Experiments 2 and 3 assessed the effect of 10 days of restraint stress on subsequent PPI tested at 30 min (Experiment 2) or 24 h (Experiment 3) following the termination of stress exposure. Experiment 3 also examined the effects of acute alcohol treatment (0.75 g/kg) on PPI in mice previously exposed to stress or no stress. Results indicate that 0.75 and 1.0 g/kg doses of alcohol increased PPI in HAP2 but not LAP2 mice. When PPI was tested 30 min after stress exposure, stressed HAP2 mice showed a trend toward decreased PPI and stressed LAP2 mice showed a trend toward increased PPI. The combination of stress and alcohol treatment did not alter PPI in either line 24 h following the termination of stress exposure, suggesting that alcohol does not ameliorate the effect of stress on PPI. Stressed LAP2 mice had increased basal circulating corticosterone on the final stress exposure day compared to non-stressed LAP2 mice, and no difference was found between stressed and non-stressed HAP2 mice. The results suggest that high genetic risk for alcoholism may be related to increased sensitivity to alcohol and stress effects on PPI, and this sensitivity could signify an endophenotype for increased genetic risk to develop alcoholism
Structural and Functional Similarity between the Bacterial Type III Secretion System Needle Protein PrgI and the Eukaryotic Apoptosis Bcl-2 Proteins
Background: Functional similarity is challenging to identify when global sequence and structure similarity is low. Activesites or functionally relevant regions are evolutionarily more stable relative to the remainder of a protein structure and provide an alternative means to identify potential functional similarity between proteins. We recently developed the FASTNMR methodology to discover biochemical functions or functional hypotheses of proteins of unknown function by experimentally identifying ligand binding sites. FAST-NMR utilizes our CPASS software and database to assign a function based on a similarity in the structure and sequence of ligand binding sites between proteins of known and unknown function.
Methodology/Principal Findings: The PrgI protein from Salmonella typhimurium forms the needle complex in the type III secretion system (T3SS). A FAST-NMR screen identified a similarity between the ligand binding sites of PrgI and the Bcl-2 apoptosis protein Bcl-xL. These ligand binding sites correlate with known protein-protein binding interfaces required for oligomerization. Both proteins form membrane pores through this oligomerization to release effector proteins to stimulate cell death. Structural analysis indicates an overlap between the PrgI structure and the pore forming motif of Bcl-xL. A sequence alignment indicates conservation between the PrgI and Bcl-xL ligand binding sites and pore formation regions. This active-site similarity was then used to verify that chelerythrine, a known Bcl-xL inhibitor, also binds PrgI.
Conclusions/Significance: A structural and functional relationship between the bacterial T3SS and eukaryotic apoptosis was identified using our FAST-NMR ligand affinity screen in combination with a bioinformatic analysis based on our CPASS program. A similarity between PrgI and Bcl-xL is not readily apparent using traditional global sequence and structure analysis, but was only identified because of conservation in ligand binding sites. These results demonstrate the unique opportunity that ligand-binding sites provide for the identification of functional relationships when global sequence and structural information is limited
Attentional Social Media: Mapping the Spaces and Networks of the Fashion Industry
In this article we use big data methods to analyze the attention paid to the fashion industry on social media. The article argues that for the fashion industry, like many industries, the core product is a form of knowledge that is dependent on gaining and holding people’s attention. To understand this attentional economy, social media offers a unique window because it is increasingly a central space within which fashion knowledge is created and shared. Using long-term, geotagged big data from Twitter, we analyze the hitherto difficult-to-explore spaces and places of the global fashion industry. The article suggests that the data confirm the ideas that there are a series of global fashion capitals that are especially important to the industry and that attention paid to fashion is highly uneven and varied across industry functions, national origins, and companies. Evidence is presented that attention to fashion is a global phenomenon that does not always directly link to where fashion products are sold. Attention to fashion is both a market-making mechanism for the industry as well as an indicator of wider social and cultural processes of tastemaking and identity formation within which fashion is entwined. The article concludes by suggesting that such data offer geographers new ways of looking at and linking economic, social, and cultural spaces and geographies and that social media analysis can help bridge boundaries that divide geographers
Living with Hepatitis C: A Vermont Needs Assessment
Background:
Hepatitis C (HCV)
Viral infection of the liver spread primarily via blood-to-blood contact (e.g., intravenous drug use (IVDU))
United States: 3.2 million chronic HCV infections (2010)
Vermont: 1.63 cases per 1000 people (2012-2013)
Barriers to Care
Exclusion of current IV drug users from HCV treatment programs despite their high rates of infection
Lack of support, causing decreased treatment adherence
Poor access to treatment: cost, transportation, competing priorities of housing, addiction management, and food
HIV and HCV
Research has shown that the multidisciplinary and integrated HIV model is appropriate for HCV
Vermont CARES
Non-profit organization that provides comprehensive services to clients with HIV in Vermonthttps://scholarworks.uvm.edu/comphp_gallery/1219/thumbnail.jp
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