Multiple elements in human β-globin locus control region 5′ HS 2 are involved in enhancer activity and position independent, transgene expression

The human β-globin Locus Control Region (LCR) has two important activities. First, the LCR opens a 200 kb chromosomal domain containing the human ε-, γ- and β-giobin genes and, secondly, these sequences function as a powerful enhancer of ε-, γ- and β-globin gene expression. Erythrold-specific, DNase I hypersensitive sites (HS) mark sequences that are critical for LCR activity. Previous experiments demonstrated that a 1.9 kb fragment containing the 5′ HS 2 site confers position-independent expression in transgenic mice and enhances human β-giobin gene expression 100-fold. Further analysis of this region demonstrates that multiple sequences are required for maximal enhancer activity; deletion of SP1, NF-E2, GATA-1 or USF binding sites significantly decrease β-globin gene expression. In contrast, no single site is required for position- independent transgene expression; all mice with site- specific mutations in 5′ HS 2 express human β-globin mRNA regardless of the site of transgene integration. Apparently, multiple combinations of protein binding sites in 5′ HS 2 are sufficient to prevent chromosomal position effects that inhibit transgene expression. © 1994 Oxford University Press

Neurocysticercosis in Oregon, 1995–2000

The unexpected death of a teenager from neurocysticercosis prompted an investigation of this disease in Oregon. We found 89 hospitalizations, 43 newly diagnosed cases, and 6 deaths from 1995 to 2000. At least five cases occurred in persons who had not traveled or lived outside the United States. Enhanced surveillance for neurocysticercosis is warranted

ATF4 Is an Oxidative Stress–Inducible, Prodeath Transcription Factor in Neurons in Vitro and in Vivo

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative death by ATF4 deletion was associated with decreased consumption of the antioxidant glutathione. Forced expression of ATF4 was sufficient to promote cell death and loss of glutathione. In ATF4(-/-) neurons, restoration of ATF4 protein expression reinstated sensitivity to oxidative death. In addition, ATF4(-/-) mice experienced significantly smaller infarcts and improved behavioral recovery as compared with wild-type mice subjected to the same reductions in blood flow in a rodent model of ischemic stroke. Collectively, these findings establish ATF4 as a redox-regulated, prodeath transcriptional activator in the nervous system that propagates death responses to oxidative stress in vitro and to stroke in vivo

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Community-associated Methicillin-resistant Staphylococcus aureus and Healthcare Risk Factors

To determine frequency of methicillin-resistant Staphylococcus aureus infections caused by strains typically associated with community-acquired infections (USA300) among persons with healthcare-related risk factors (HRFs), we evaluated surveillance data. Of patients with HRFs, 18%–28% had a "community-associated" strain, primarily USA300; of patients without HRFs, 26% had a "healthcare-associated" strain, typically USA100

Hyptiogastrites electrinus Cockerell, 1917, from Myanmar (Burmese) amber: Redescription and its placement within the Evanioidea (Insecta: Hymenoptera)

© The Natural History MuseumThe wasp Hyptiogastrites electrinus Cockerell, 1917, from the Lower Cretaceous (Upper Albian) Myanmar (Burmese) amber is redescribed from the well-preserved holotype and its relationship with extant Aulacidae and Gasteruptiidae (Hymenoptera: Evanioidea) evaluated. Although the wing venation is identical to the majority of extant Hyptiogastrinae (Gasteruptiidae), phylogenetic analysis places H. electrinus as sister taxon to the Aulacidae s.str., (i.e. Aulacus + Pristaulacus). Thus, Hyptiogastrinae is confirmed as having a restricted Southern Hemisphere distribution (i.e. Australasia and South America). Consistent with this result, H. electrinus is included within a slightly more broadly defined Aulacidae rather than being placed in a new monotypic family. Characters that align this species with the Aulacidae include: having small circular eyes, percurrent Y-shaped notauli, pyramidal shape of the propodeum and the presence of a groove or ovipositor guide on the hind coxae.John T. Jennings, Andrew D. Austin and Nicholas B. Steven

Establishment of a Statewide Network for Carbapenem-Resistant Enterobacteriaceae Prevention in a Low-Incidence Region

OBJECTIVE: To establish a statewide network to detect, control, and prevent the spread of carbapenem-resistant Enterobacteriaceae (CRE) in a region with a low incidence of CRE infection. DESIGN: Implementation of the Drug Resistant Organism Prevention and Coordinated Regional Epidemiology (DROP-CRE) Network. SETTING AND PARTICIPANTS: Oregon infection prevention and microbiology laboratory personnel, including 48 microbiology laboratories, 62 acute care facilities, and 140 long-term care facilities. METHODS: The DROP-CRE working group, comprising representatives from academic institutions and public health, convened an interdisciplinary advisory committee to assist with planning and implementation of CRE epidemiology and control efforts. The working group established a statewide CRE definition and surveillance plan; increased the state laboratory capacity to perform the modified Hodge test and polymerase chain reaction for carbapenemases in real time; and administered surveys that assessed the needs and capabilities of Oregon infection prevention and laboratory personnel. Results of these inquiries informed CRE education and the response plan. RESULTS: Of 60 CRE reported from November 2010 through April 2013, only 3 were identified as carbapenemase producers; the cases were not linked, and no secondary transmission was found. Microbiology laboratories, acute care facilities, and long-term care facilities reported lacking carbapenemase testing capability, reliable interfacility communication, and CRE awareness, respectively. Survey findings informed the creation of the Oregon CRE Toolkit, a state-specific CRE guide booklet. CONCLUSIONS: A regional epidemiology surveillance and response network has been implemented in Oregon in advance of widespread CRE transmission. Prospective surveillance will determine whether this collaborative approach will be successful at forestalling the emergence of this important healthcare-associated pathogen.This is the publisher’s final pdf. The published article is copyrighted by the University of Chicago Press on behalf of the Society for Healthcare Epidemiology of America and can be found at: http://www.press.uchicago.edu/ucp/journals/journal/iche.html

Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects.Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection.DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD