Two Factors that Bind to Highly Conserved Sequences in Mammalian Type C Retroviral Enhancers.

The transcriptional enhancers of the Moloney and Friend murine leukemia viruses (MLV) are important determinants of viral pathogenicity. We used electrophoretic mobility shift and methylation interference assays to study nuclear factors which bind to a region of these enhancers whose sequence is identical between Moloney and Friend viruses and particularly highly conserved among 35 mammalian type C retroviruses whose enhancer sequences have been aligned (E. Golemis, N. A. Speck, and N. Hopkins, J. Virol. 64:534-542, 1990). Previous studies identified sites for the leukemia virus factor b (LVb) and core proteins in this region (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987) as well as a site, overlapping those for LVb and core, for a third factor (N. R. Manley, M. A. O\u27Connell, P. A. Sharp, and N. Hopkins, J. Virol. 63:4210-4223, 1989). Surprisingly, the latter factor appeared to also bind two sites identified in the Friend MLV enhancer, Friend virus factor a and b1 (FVa and FVb1) sites, although the sequence basis for the ability of the protein to bind these diverse sites was not apparent. Here we describe the further characterization of this binding activity, termed MCREF-1 (for mammalian type C retrovirus enhancer factor 1), and the identification of a consensus sequence for its binding, GGN8GG. We also identify a factor, abundant in mouse T-cell lines and designated LVt, which binds to two sites in the Moloney MLV enhancer, overlapping the previously identified LVb and LVc binding sites. These sites contain the consensus binding site for the Ets family of proteins. We speculate on how distinct arrays of these factors may influence the disease-inducing phenotype

The Task Force Initiative: Local Interventions at the Department Level—A Key Component of a Multi-tiered Approach to Promote Institutional Change

This NIH Transforming Academic Culture (NIH-TAC) trial is a multi-level coordinated intervention to enhance institutional culture, increase academic productivity, and improve job satisfaction for women faculty. This poster details a task force initiative in which each department and division reviewed their current practices and policies to recommend and implement change. This particular task force resulted in a list of interventions which were disseminated and implemented throughout the institution

Baseline Repeated Measures from Controlled Human Exposure Studies: Associations between Ambient Air Pollution Exposure and the Systemic Inflammatory Biomarkers IL-6 and Fibrinogen

Introduction: Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardiovascular disease. Objective: We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. Methods: In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5). Linear mixed-model regression determined the effects of the pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. Results: We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.08–0.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.06–0.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. Conclusions: This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response

Preoperative Screening and Case Cancellation in Cocaine-Abusing Veterans Scheduled for Elective Surgery

Background. Perioperative management of cocaine-abusing patients scheduled for elective surgery varies widely based on individual anecdotes and personal experience. Methods. Chiefs of the anesthesia departments in the Veterans Affairs (VA) health system were surveyed to estimate how often they encounter surgical patients with cocaine use. Respondents were asked about their screening criteria, timing of screening, action resulting from positive screening, and if they have a formal policy for management of these patients. Interest in the development of VA guidelines for the perioperative management of patients with a history of cocaine use was also queried. Results. 172 VA anesthesia departments’ chiefs were surveyed. Response rate was 62%. Over half of the facilities see cocaine-abusing patients at least once a week (52%). Two thirds of respondents canceled or delayed patients with a positive screen regardless of clinical symptoms. Only eleven facilities (10.6%) have a formal policy. The majority of facilities (80%) thought that having formal guidelines for perioperative management of cocaine-abusing patients would be helpful to some extent. Results. 172 VA anesthesia departments’ chiefs were surveyed. Response rate was 62%. Over half of the facilities see cocaine-abusing patients at least once a week (52%). Two thirds of respondents canceled or delayed patients with a positive screen regardless of clinical symptoms. Only eleven facilities (10.6%) have a formal policy. The majority of facilities (80%) thought that having formal guidelines for perioperative management of cocaine-abusing patients would be helpful to some extent. Conclusions. There is a general consensus that formal guidelines would be helpful. Further studies are needed to help formulate evidence-based guidelines for managing patients screening positive for cocaine prior to elective surgery

DNA Hypomethylation, Ambient Particulate Matter, and Increased Blood Pressure: Findings From Controlled Human Exposure Experiments

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144592/1/jah3232.pd

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells

Abstract Background Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. Results Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time. Conclusions Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice

Controlled Exposure Study of Air Pollution and T-Wave Alternans in Volunteers without Cardiovascular Disease

Background: Epidemiological studies have assessed T-wave alternans (TWA) as a possible mechanism of cardiac arrhythmias related to air pollution in high-risk subjects and have reported associations with increased TWA magnitude. Objective: In this controlled human exposure study, we assessed the impact of exposure to concentrated ambient particulate matter (CAP) and ozone (O:3) on T-wave alternans in resting volunteers without preexisting cardiovascular disease. Methods: Seventeen participants without preexisting cardiovascular disease were randomized to filtered air (FA), CAP (150 μg/m3), O3 (120 ppb), or combined CAP + O3 exposures for 2 hr. Continuous electrocardiograms (ECGs) were recorded at rest and T-wave alternans (TWA) was computed by modified moving average analysis with QRS alignment for the artifact-free intervals of 20 beats along the V2 and V5 leads. Exposure-induced changes in the highest TWA magnitude (TWAMax) were estimated for the first and last 5 min of each exposure (TWAMax_Early and TWAMax_Late respectively). ΔTWAMax (Late–Early) were compared among exposure groups using analysis of variance. Results: Mean ± SD values for ΔTWA:Max were –2.1 ± 0.4, –2.7 ± 1.1, –1.9 ± 1.5, and –1.2 ± 1.5 in FA, CAP, O3, and CAP + O3 exposure groups, respectively. No significant differences were observed between pollutant exposures and FA. Conclusion: In our study of 17 volunteers who had no preexisting cardiovascular disease, we did not observe significant changes in T-wave alternans after 2-hr exposures to CAP, O:3, or combined CAP + O3. This finding, however, does not preclude the possibility of pollution-related effects on TWA at elevated heart rates, such as during exercise, or the possibility of delayed responses

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis

Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this

Self-organisation in LTE networks : an investigation

Mobile telecommunications networks based on Long Term Evolution (LTE) technology promise faster throughput to their users. LTE networks are however susceptible to a phenomenon known as inter-cell interference which can greatly reduce the throughput of the network causing unacceptable degradation of performance for cell edge users. A number of approaches to mitigating or minimising inter-cell interference have been presented in the literature such as randomisation, cancellation and coordination. The possibility of coordination between network nodes in an LTE network is made possible through the introduction of the X2 network link. This thesis explores approaches to reducing the effect of inter-cell interference on the throughput of LTE networks by using the X2 link to coordinate the scheduling of radio resources. Three approaches to the reduction of inter-cell interference were developed. Localised organisation is a centralised scheme in which a scheduler is optimised by a Genetic Algorithm (GA) to reduce interference. Networked organisation makes use of the X2 communications link to enable the network nodes to exchange scheduling information in a way that lowers the level of interference across the whole network. Finally a more distributed and de-centralised approach is taken in which each of the network nodes optimises its own scheduling in coordination with its neighbours. An LTE network simulator was built to allow for experimental comparison between these techniques and a number of existing approaches and to serve as a test bed for future algorithm development. These approaches were found to significantly improve the throughput of the cell edge users who were most affected by intereference. In particular the networked aspect of these approaches yielded the best initial results showing clear improvement over the existing state of the art. The distributed approach shows significant promise given further development.EPSR