Regulation of the yeast transcriptional activator ADR1

Glucose repression of the ADH2 gene from Saccharomyces cerevisiae is mediated by the abundance and activity of the transcriptional activator ADR1. The focus of this dissertation is to characterize the mechanisms by which glucose controls the ability of ADR1 to activate ADH2 transcription. Glucose results in a two-fold decrease in the steady state levels of ADR1 mRNA. This glucose-dependent reduction in steady state ADR1 mRNA was shown to be due to an increased rate of ADR1 mRNA degradation. The unusually long, 510 nucleotide 5\sp\prime untranslated region of the ADR1 mRNA appeared to mediate this glucose-dependent ADR1 mRNA decay. To better understand the posttranslational control of ADR1 activity by glucose, the ADR1\sp{c} mutations which allow glucose-insensitive ADH2 expression were analyzed. The mechanism by which three mutated genes (saf1, saf2, and saf3) suppressed the ADR1\sp{c} phenotype was investigated. Each of the mutated saf genes was found to suppress ADR1\sp{\rm c} activity by reducing ADR1\sp{c} transcription 5- to 8-fold under glucose growth conditions. The SAF genes were also required for ADR1 transcription under glucose conditions, indicating that these genes are not specifically involved in ADR1\sp{\rm c} function. A deletion analysis conducted on an ADR1\sp{\rm c} protein indicated that no ADR1 residues outside the site of the ADR1\sp{\rm c} mutations were specifically required for ADR1\sp{\rm c} function. ADR1\sp{c} mutations enhanced the activity of ADR1 proteins that contained either of two separate activation domains. Deletion analysis also allowed for the improved mapping of the functional domains in ADR1. ADR1 was found to contain multiple domains required for transcriptional activation, and these activation domains were found to be separated by residues that inhibit activation. One inhibitory region encompasses the site of the ADR1\sp{\rm c} mutations. This array of alternating activating and inhibitory regions in ADR1 suggests that ADR1 activity is modulated by interactions between different positive and negative domains in ADR1

Myeloid-Derived Suppressor Cells in Murine Retrovirus-Induced AIDS Inhibit T- and B-Cell Responses In Vitro That Are Used To Define the Immunodeficiency

Myeloid-derived suppressor cells (MDSCs) have been characterized in several disease settings, especially in many tumor systems. Compared to their involvement in tumor microenvironments, however, MDSCs have been less well studied in their responses to infectious disease processes, in particular to retroviruses that induce immunodeficiency. Here, we demonstrate for the first time the development of a highly immunosuppressive MDSC population that is dependent on infection by the LP-BM5 retrovirus, which causes murine acquired immunodeficiency. These MDSCs express a cell surface marker signature (CD11b Gr-1 Ly6C ) characteristic of monocyte-type MDSCs. Such MDSCs profoundly inhibit immune responsiveness by a cell dose- and substan- tially inducible nitric oxide synthase (iNOS)-dependent mechanism that is independent of arginase activity, PD-1–PD-L1 ex- pression, and interleukin 10 (IL-10) production. These MDSCs display levels of immunosuppressive function in parallel with the extent of disease in LP-BM5-infected wild-type (w.t.) versus knockout mouse strains that are differentially susceptible to patho- genesis. These MDSCs suppressed not only T-cell but also B-cell responses, which are an understudied target for MDSC inhibi- tion. The MDSC immunosuppression of B-cell responses was confirmed by the use of purified B responder cells, multiple B-cell stimuli, and independent assays measuring B-cell expansion. Retroviral load measurements indicated that the suppressive Ly6Glow/ Ly6C CD11b -enriched MDSC subset was positive for LP-BM5, albeit at a significantly lower level than that of non- fractionated splenocytes from LP-BM5-infected mice. These results, including the strong direct MDSC inhibition of B-cell re- sponsiveness, are novel for murine retrovirus-induced immunosuppression and, as this broadly suppressive function mirrors that of the LP-BM5-induced disease syndrome, support a possible pathogenic effector role for these retrovirus-induced MDSCs

How OBGYNs can assist in the prenatal care and delivery of western lowland gorillas

Prenatal care and perinatal planning are paramount for successful delivery outcomes in human pregnancies and has been shown to be equally as important with non-human primates. The authors describe two pregnancies and deliveries of a 12-year-old primigravid western lowland gorilla, Macy. Macy’s first pregnancy resulted in a stillbirth and was complicated by breech positioning, while her second pregnancy resulted in a viable infant. This case report outlines the prenatal care Macy received in her pregnancies and highlights the importance of ultrasound for dating and fetal evaluation. The authors discuss options for breech positioning and considerations for cesarean section. This article showcases how obstetricians and veterinarians can implement human obstetrical recommendations with non-human primates to improve delivery outcomes. 

The CD154/CD40 Interaction Required for Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated by Upregulation of the CD80/CD86 Costimulatory Molecules

C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40−/− and CD154−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4+ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86−/− B6 mice develop MAIDS after LP-BM5 infection

HEY LARRY! INVESTIGATING INTERRUPTIONS IN FUTURE VERTICAL LIFT PLATFORMS

Using technology to improve human performance is critical to maximizing the benefits of future combat systems. This study explores the effects of interruptions during high and low cognitive load states when completing dynamic tasks. Furthermore, it provides insight into how to integrate artificial intelligence and virtual assistants into future aircraft effectively. This research and the following analysis provided the Holistic Situation Awareness and Decision Making (HSA-DM) program office with meaningful data and recommendations that will enable them to reduce the impact of interruptions while improving the performance of future pilots. Specifically, this study collected and examined heart rate variability, subjective cognitive load, flight metrics, interruption lag, and task resumption lag while participants piloted an aircraft and performed dynamic tasks in a flight simulator. There were three different modalities used to assist participants with completing interrupted tasks while performing their primary task. The research team determined that the tactile activated artificial intelligence was the most effective at reducing total interruption time while having the smallest effects on flight performance and cognitive load.Major, United States ArmyMajor, United States ArmyCaptain, United States ArmyCaptain, United States ArmyCaptain, United States ArmyApproved for public release. Distribution is unlimited

An Instrument to Enable Identification of Anthropogenic CO2 Emissions Using Concurrent CO Measurements

We have developed an instrument concept that will enable the measurement of CO from the top of the atmosphere to the Earth's surface with very high sensitivity and at the high spatial and temporal resolutions required by the NRC Decadal Survey mission Active Sensing of Carbon Dioxide (CO2) over Nights, Days and Seasons (ASCENDS). We are developing an innovative CO sensor that will enable the ASCENDS mission to differentiate between anthropogenic and natural sources and sinks of global carbon. The NRC Decadal Survey places particular emphasis on retrieving CO information for the planetary boundary layer. Measurement made using both the 2.3 micron and 4.7 micron channels are needed to achieve the sensitivity required in the lower atmosphere where the degree of CO - CO2 correlation is indicative of anthropogenic sources of CO2. Measurements made using only the 4.7 micron channel cannot provide sufficient sensitivity to CO in the very lowest layers of the atmosphere. The fundamental method we use is Gas Filter Correlation Radiometry (GFCR), a highly successful technique used in other airborne and space-based missions for detecting trace species in the Earth's atmosphere. Our version of GFCR overcomes many of the limitations encountered by prior and existing instruments, allowing us to measure weak signals from small targets very quickly and with extremely high specificity by employing a new dual beam radiometer concept using a focal plane array. Our design will provide a means to make the desired CO measurements for the ASCENDS mission. A simple change in gas filter cell contents would allow the same hardware to measure CH4 with high precision under the nominal ASCENDS mission spatial and temporal constraints. All critical components in the sensor design are mature, many subsystems tested, and the system has been extensively modeled, bringing it to a present Technology Readiness Level (TRL) of 3 (though some individual components are at TRLs 6-9). We are presently developing critical components for the new spectrometer and advancing our understanding of the measurement requirements for both CO and CH4. This new GFCR technique/sensor will enable measurements of trace gases with high sensitivity while maintaining the inherent robustness and simplicity of the more traditional radiometer hardware. Initial estimates of cost/risk of a spacebased 2-channel GFCR indicate that our design is extremely cost effective and will fit within existing ASCENDS mission budget constraints as determined by the NRC Decadal Survey and a NASA-sponsored mission study

Evaluating Learner Perceptions of Use of Simulations for New nurses – A Collaboration Between the UT SON and the Methodist Hospital

The purpose of this evaluation project was to describe the integration of simulation into a nursing internship program and to help prepare new graduate nurses for patient care. Additionally, learning styles and perceptions of active learning, collaboration among peers, ways of learning, expectation of simulation, satisfaction, self-confidence, and design of simulation were examined. [See PDF for complete abstract

The Ursinus Weekly, October 13, 1905

School of Theology • Football • Oyster supper • Society notes • College notes • Alumni • Ursinus Union • College world • Camp reunion • Literary Supplement: A plea for the children; Cut from life; Ludwig van Beethoven; Youth\u27s passion; A distinctive American literature; Experience of a View Agent; Carpe diem; Integrity in political life • Exchangeshttps://digitalcommons.ursinus.edu/weekly/2952/thumbnail.jp