Role of LBPA and Alix in multivesicular liposome formation and endosome organization

What are the components that control the assembly of subcellular organelles in eukaryotic cells? Although membranes can clearly be distorted by cytosolic factors, very little is known about the intrinsic mechanisms that control the biogenesis, shape, and organization of organellar membranes. Here, we found that the unconventional phospholipid lysobisphosphatidic acid (LBPA) could induce the formation of multivesicular liposomes that resembled the multivesicular endosomes that exist where this lipid is found in vivo. This process depended on the same pH gradient that exists across endosome membranes in vivo and was selectively controlled by Alix. In turn, Alix regulated the organization of LBPA-containing endosomes in vivo.

Antisense transcription in the mammalian transcriptome

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring genes in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

Regulated localization of rab18 to lipid droplets - Effects of lipolytic stimulation and inhibition of lipid droplet catabolism

Rab GTPases are crucial regulators of membrane traffic. Here we have examined a possible association of Rab proteins with lipid droplets (LDs), neutral lipid-containing organelles surrounded by a phospholipid monolayer, also known as lipid bodies, which have been traditionally considered relatively inert storage organelles. Although we found close apposition between LDs and endosomal compartments labeled by expressed Rab5, Rab7, or Rab11 constructs, there was no detectable labeling of the LD surface itself by these Rab proteins. In contrast, GFP-Rab18 localized to LDs and immunoelectron microscopy showed direct association with the monolayer surface. Green fluorescent protein (GFP)-Rab18-labeled LDs underwent oscillatory movements in a localized area as well as sporadic, rapid, saltatory movements both in the periphery of the cell and toward the perinuclear region. In both adipocytes and non-adipocyte cell lines Rab18 localized to a subset of LDs. To gain insights into this specific localization, Rab18 was co-expressed with Cav3(DGV), a truncation mutant of caveolin-3 shown to inhibit the catabolism and motility of lipid droplets. GFP-Rab18 and mRFP-Cav3(DGV) labeled mutually exclusive subpopulations of LDs. Moreover, in 3T3-L1 adipocytes, stimulation of lipolysis increased the localization of Rab18 to LDs, an effect reversed by beta-adrenergic antagonists. These results show that a Rab protein localizes directly to the monolayer surface of LDs. In addition, association with the LD surface was increased following stimulation of lipolysis and inhibited by a caveolin mutant suggesting that recruitment of Rab18 is regulated by the metabolic state of individual LDs.

A role for the phagosome in cytokine secretion

Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor alpha (TNF alpha) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNF alpha and expands the membrane for phagocytosis.

A planning model for needs analysis for subacute care

The purpose of this study is to produce a model to be used by state regulating agencies to assess demand for subacute care. In accomplishing this goal, the study refines the definition of subacute care, demonstrates a method for bed need assessment, and measures the effectiveness of this new level of care. This was the largest study of subacute care to date. Research focused on 19 subacute units in 16 states, each of which provides high-intensity rehabilitative and/or restorative care carried out in a high-tech unit. Each of the facilities was based in a nursing home, but utilized separate staff, equipment, and services. Because these facilities are under local control, it was possible to study regional differences in subacute care demand.^ Using this data, a model for predicting demand for subacute care services was created, building on earlier models submitted by John Whitman for the American Hospital Association and Robin E. MacStravic. The Broderick model uses the "bootstrapping" method and takes advantage of high technology: computers and software, databases in business and government, publicly available databases from providers or commercial vendors, professional organizations, and other information sources. Using newly available sources of information, this new model addresses the problems and needs of health care planners as they approach the challenges of the 21st century. ^

Essays on the determinants of private investment: The effects of relative price uncertainty and political instability

The objective of this study was to provide empirical evidence on the effects of relative price uncertainty and political instability on private investment. My effort is expressed in a single-equation model using macroeconomic and socio-political data from eight Latin American countries for the period 1970–1996. Relative price uncertainty is measured by the implied volatility of the exchange rate and political instability is measured by using indicators of social unrest and political violence. ^ I found that, after controlling for other variables, relative price uncertainty and political instability are negatively associated with private investment. Macroeconomic and political stability are key ingredients for the achievement of a strong investment response. This highlights the need to develop the state and build a civil society in which citizens can participate in decision-making and express consent without generating social turmoil. At the same time the government needs to implement structural policies along with relative price adjustments to eliminate excess volatility in price movements in order to provide a stable environment for investment. ^

Tocqueville in Miami: Political culture and political organizing in Miami's Cuban community

This study examines the effectiveness of civic organizations focusing on leadership and the role of culture in politics. The study is based on a quasi-experimental research design and relies primarily on qualitative data. The study focuses on Miami's Cuban community in order to examine the role of public initiative in grassroots civic and community organizations. ^ The Miami Cuban community is a large, institutionally complex and cohesive ethnic community with dense networks of community organizations. The political and economic success of the community makes it an opportune setting for a study of civic organizing. The sheer number of civic organizations to be found in Miami's Cuban community suggests that the community's civic organizations have something to do with the considerable vibrancy and civic capacity of the community. How have the organizations managed to be so successful over so many years and what can be learned about successful civic organizing from their experience?^ Civic organizations in Miami's Cuban community are overwhelmingly ethnic-based organizations. The organizations recreate collective symbols that come from community members' memories of and attachments to the place of origin they hold dear as ethnic Cubans. They recreate a collective Cuban past that community members remember and that is the very basis of the community to which they belong.^ Cuban Miami's ethnically based civic organizations have generally performed better than the literature on civic organizations says they should. They gained greater access to community ties and social capital, and they exhibited greater organizational longevity. The fit between the political culture of civic organizations and that of the broader political community helps to explain this success. Yet they do not perform in the same way or in support of the same social purposes. Some stress individual agency rather than community agency, and some pursue an externally-oriented social purpose, whereas others focus on building an internal community.^

The American politics of a Jewish Judea and Samaria

This dissertation poses a set of six questions about one of the Israel Lobby's particular components, a Potential Christian Jewish coalition (PCJc) within American politics that advocates for Israeli sovereignty over "Judea and Samaria" ("the West Bank"). The study addresses: the profiles of the individuals of the PCJc; its policy positions, the issues that have divided it, and what has prevented, and continues to prevent, the coalition from being absorbed into one or more of the more formally organized components of the Israel Lobby; the resources and methods this coalition has used to attempt to influence U.S. policy on (a) the Middle East, and (b) the Arab-Israeli conflict in particular; the successes or failures of this coalition's advocacy and why it has not organized; and what this case reveals about interest group politics and social movements in the United States. This dissertation follows the descriptive-analytic case-study tradition that comprises a detailed analysis of a specific interest group and one policy issue, which conforms to my interest in the potential Christian Jewish coalition that supports a Jewish Judea and Samaria. I have employed participant observation, interviewing, content analysis and documentary research. The findings suggest: The PCJc consists of Christian Zionists and mostly Jews of the center religious denominations. Orthodox Jewish traditions of separation from Christians inhibit like-minded Christians and Jews from organizing. The PCJc opposes an Arab state in Judea and Samaria, and is not absorbed into more formally organized interest groups that support that policy. The PCJc's resources consist of support and funding from conservatives. Methods include use of education, debates and media. Members of the PCJc are successful because they persist in their support for a Jewish Judea and Samaria and meet through other organizations around Judeo-Christian values. The PCJc is deterred from advocacy and organization by a mobilization of bias from a subgovernment in Washington, D.C. comprising Congress, the Executive branch and lobby organizations. The study's results raise questions about interest group politics in America and the degree to which the U.S. political system is pluralistic, suggesting that executive power constrains the agenda to "safe" positions it favors.

The Continuing Significance of Exile in American Politics

Dr. Nicol Rae, Dean of the College of Letters and Science and Professor of Political Science at Montana State University, speaks of the U.S. receptiveness towards professors who have exiled from other nations.