55 research outputs found
A Spatiotemporal Notch Interaction Map From Plasma Membrane to Nucleus
Notch signaling relies on ligand-induced proteolysis of the transmembrane receptor Notch to liberate a nuclear effector that drives cell fate decisions. Upon ligand binding, sequential cleavage of Notch by the transmembrane protease ADAM10 and the intracellular protease γ-secretase releases the Notch intracellular domain (NICD), which translocates to the nucleus and forms a complex that induces target gene transcription. To map the location and timing of the individual steps required for the proteolysis and movement of Notch from the plasma membrane to the nucleus, we used proximity labeling with quantitative, multiplexed mass spectrometry to monitor the interaction partners of endogenous NOTCH2 after ligand stimulation in the presence of a γ-secretase inhibitor and as a function of time after inhibitor removal. Our studies showed that γ-secretase-mediated cleavage of NOTCH2 occurred in an intracellular compartment and that formation of nuclear complexes and recruitment of chromatin-modifying enzymes occurred within 45 min of inhibitor washout. These findings provide a detailed spatiotemporal map tracking the path of Notch from the plasma membrane to the nucleus and identify signaling events that are potential targets for modulating Notch activity
HIV and Tuberculosis Trends in the United States and Select Sub-Saharan Africa Countries
Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) are two catastrophic diseases affecting millions of people worldwide every year; and are considered to be pandemic by the World Health Organization. This study aims to compare the recent trends in TB and HIV in the United States and Sub-Saharan African Countries. Data (incidence, prevalence and death rates of HIV and TB) for the United States, Cameroon, Nigeria, and South Africa were collected from The Joint United Nations Programme for HIV/AIDS (UNAIDS), US Census Bureau and World Health Organization (WHO) databases and analyzed using Statistical Analysis Software (SAS v 9.1). Analysis of Variance (ANOVA) was performed to compare the variables of interest between the countries and across time. Results showed that percent rates of TB cases, TB deaths, HIV cases and HIV deaths were significantly different (P < 0.001) among these countries from 1993 to 2006. South Africa had the highest rates of HIV and TB; while US had the lowest rates of both diseases. Tuberculosis and HIV rates for Cameroon and Nigeria were significantly higher when compared to the United States, but were significantly lower when compared to South Africa (P < 0.001). There were significant differences (P < 0.001) in the prevalence of TB and HIV between the United States and the Sub-Saharan African countries, as well as differences within the Sub-Saharan African countries from 1993 to 2006. More analysis needs to be carried out in order to determine the prevalence and incidence of HIV and TB among multiple variables like gender, race, sexual orientation and age to get a comprehensive picture of the trends of HIV and TB
Phoenix Mars Scout UHF Relay-Only Operations
The Phoenix Mars Scout Lander will launch in August 2007 and land on the northern plains of Mars in May of 2008. In a departure from traditional planetary surface mission operations, it will have no direct-to-Earth communications capability and will rely entirely on Mars-orbiting relays in order to facilitate command and control as well as the return of science and engineering data. The Mars Exploration Rover missions have demonstrated the robust data-return capability using this architecture, and also have demonstrated the capability of using this method for command and control. The Phoenix mission will take the next step and incorporate this as the sole communications link. Operations for 90 Sols will need to work within the constraints of Odyssey and Mars Reconnaissance Orbiter communications availability, anomalies must be diagnosed and responded to through an intermediary and on-board fault responses must be tolerant to loss of a relay. These and other issues pose interesting challenges and changes in paradigm for traditional space operations and spacecraft architecture, and the approach proposed for the Phoenix mission is detailed herein
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Argonne National Laboratory Report ANL-5715
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Seroprevalence of Chagas disease in Ushuaia, Argentina, an area without Triatominae
Fil: Mallimaci, María Cristina. Servicio de Laboratorio, Hospital Regional Ushuaia; Argentina.Fil: Sijvarger, Carina. Servicio de Laboratorio, Hospital Regional Ushuaia; Argentina.Fil: Dates, A. Servicio de Hemoterapia, Hospital Regional Ushuaia; Argentina.Fil: Alvarez, M. Servicio de Laboratorio, Hospital Regional Ushuaia; Argentina.Fil: Sosa-Estani, S. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Determine the seroprevalence of Trypanosoma cruzi infection in Ushuaia, Argentina, which is the southernmost city in the world
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