A Kinder, Gentler Student Body

Monica Viega describes what went on in her classroom earlier in the school year as Jerry Springer fights. Displays of anger and incivility among the 5th graders sometimes grew so intense that furniture would get tossed across the room. But the scene in Ms. Viega\u27s classroom no longer resembles a raucous daytime talk show. Every morning, her Blalock Elementary School students sit in a circle and discuss how they treat one another. They talk about what they see on the television news and about keeping drugs and violence out of their neighborhoods. This amazes me, Ms. Viega, a first-year teacher, said before the end of school this spring. These are tough kids. I used to have to pull them apart. She and other staff members credit the school\u27s three-year involvement in a character education project with making Blalock a less hostile place. The 540-student school, part of the Atlanta school system, serves the Bankhead Courts housing project on this city\u27s northwest side. It is one of 28 pilot sites in the state to receive grants from the Georgia Humanities Council to develop a character education program. Blalock\u27s program has received funding since 1996

The Great Depression and Its Impact on an Emerging Research Library: The University of North Carolina Library, 1929-1941

In the years after World War I, the University of North Carolina (UNC) transformed itself from a respectable, but provincial, academic institution to a true research university, becoming in 1922 only the second university in the South to be admitted to the Association of American Universities. The development of the library was part of that transformation, and the dedication of a new library building on October 19, 1929 can be seen as the symbolic high-water mark of a period of growth and maturation for the university. On that sunny Saturday in Chapel Hill, the university band led a group of dignitaries, alumni, and well-wishers into Memorial Hall for a program officially dedicating the new library. University president Harry Woodburn Chase presided. North Carolina governor O. Max Gardner presented the building to the university; John Sprunt Hill, chairman of the trustee building committee and a long-time library supporter, accepted it. Andrew Keogh, Yale University librarian and American Library Association president, delivered the dedication address

Transfer student analysis and retention: a collaborative endeavor

This paper aims to describe a multifaceted campus-wide initiative to retain transfer students that was undertaken when it was recognized that their retention rates were lower than those of first-time, full-time students. The “all-hands-on-deck” approach described in this paper demonstrates how strategic collaborations among the many institutional stakeholders at a public research university were marshalled to have a significant and positive impact on student retention

Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential

Changes in insulin sensitivity over time and associated factors in HIV-infected adolescents

OBJECTIVE: To compare prevalence of insulin resistance between perinatally HIV-infected (PHIV+) and perinatally HIV-exposed, but uninfected adolescents (PHEU), determine incidence of and contributory factors to new and resolved cases of insulin resistance in PHIV+, and evaluate glucose metabolism. DESIGN: Cross-sectional design for comparison of prevalence among PHIV+ and PHEU. Longitudinal design for incidence and resolution of insulin resistance among PHIV+ at risk for these outcomes. METHODS: The source population was adolescents from pediatric HIV clinics in the United States and Puerto Rico participating in the Pediatric HIV/AIDS Cohort Study, an ongoing prospective cohort study designed to evaluate impact of HIV infection and its treatment on multiple domains in preadolescents and adolescents. Insulin resistance was assessed by homeostatic model assessment of insulin resistance. Those with incident insulin resistance underwent 2-h oral glucose tolerance test and HbA1c. Baseline demographic, metabolic, and HIV-specific variables were evaluated for association with incident or resolved insulin resistance. RESULTS: Unadjusted prevalence of insulin resistance in PHIV+ was 27.3 versus 34.1% in PHEU. After adjustment for Tanner stage, age, sex, and race/ethnicity, there was no significant difference between groups. Factors positively associated with developing insulin resistance included female sex, higher BMI z score, and higher waist circumference; those associated with resolving insulin resistance included male sex and lower BMI z score. CONCLUSION: Prevalence of insulin resistance in PHIV+ and PHEU was substantially higher than that reported in HIV-uninfected nonoverweight youth, but similar to that in HIV-uninfected obese youth. Factors associated with incident or resolved insulin resistance among PHIV+ were similar to those reported in HIV-negative obese youth. However, a contributory role of HIV infection and/or its treatment to the incident risk of insulin resistance cannot be excluded

Structural and Thermodynamic Basis for Enhanced DNA Binding by a Promiscuous Mutant EcoRI Endonuclease

Promiscuous mutant EcoRI endonucleases bind to the canonical site GAATTC more tightly than does the wild-type endonuclease, yet cleave variant (EcoRI*) sites more rapidly than does wild-type. The crystal structure of the A138T promiscuous mutant homodimer in complex with a GAATTC site is nearly identical to that of the wild-type complex, except that the Thr138 side chains make novel packing interactions with bases in the 5′-flanking regions outside the recognition hexanucleotide, while excluding two bound water molecules seen in the wild-type complex. Molecular dynamics simulations confirm exclusion of these waters. The structure and simulations suggest multiple possible reasons why binding of A138T protein to the GAATTC site has ΔS° more favorable and ΔH° less favorable than for wild-type endonuclease binding. The novel interactions of Thr138 with flanking bases may permit A138T, unlike wild-type enzyme, to form complexes with EcoRI* sites that structurally resemble the specific wild-type complex with GAATTC

Fixed-Combination Halobetasol Propionate and Tazarotene in the Treatment of Psoriasis: Narrative Review of Mechanisms of Action and Therapeutic Benefits

Psoriasis is a lifelong disease associated with cycles of remission and relapse. Topical treatments are the front line of psoriasis therapy for most patients and have antiproliferative, anti-inflammatory, and immunosuppressive mechanisms of action. Novel fixed-dose combinations of topical therapeutic agents are becoming increasingly available, leveraging multiple mechanisms of action to improve safety and efficacy with formulations that are easier to use and may allow for the use of lower doses of active ingredients. A fixed-combination lotion containing the potent-to-super-potent corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (HP 0.01%/TAZ 0.045%) was recently developed using polymeric emulsion technology. This new formulation technology allows for more uniform and efficient delivery of the active ingredients at lower doses than conventional monotherapy formulations of either ingredient while providing enhanced hydration and moisturization. This review provides an up-to-date overview of the therapeutic mechanisms of action of HP and TAZ, the rationale behind the development of HP 0.01%/TAZ 0.045% lotion, and clinical trials data on the efficacy, safety and tolerability, and maintenance of therapeutic effect with HP 0.01%/TAZ 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis

Biomarkers of aging in Drosophila

Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging-related damage. Using this approach, we assessed several commonly used biomarkers of aging-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging-related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging-related damage. Our approach provides a powerful method for identification of biomarkers of aging.This work was supported by the Wellcome Trust and in part by I+D grants from the Spanish Ministry of Education and Science (BFU2006-14495 ⁄ BFI), the Spanish Ministry of Health (ISCIII, Red de Envejecimiento y Fragilidad, RD06 ⁄ 0013 ⁄ 0012), and the Generalitat of Catalunya (2005SGR00101) to R.P; the Spanish Ministry of Health (FIS PI081843), Spanish Ministry of Education and Science (AGL2006-12433), and ‘‘La Caixa’’ Foundation to M.P.O. Also supported by the Max Planck Society (J.J. and L.P), COST B-35 Action; Research into Ageing (A.J.L.) and the Medical Research Council and National Institutes of Health (P01 AG025901, PL1 AG032118 and P30 AG025708) (M.D.B.)

Clinical implications of circulating tumor cells of breast cancer patients: role of epithelial-mesenchymal plasticity

There is increasing interest in circulating tumor cells (CTCs) due to their purported role in breast cancer metastasis, and their potential as a “liquid biopsy” tool in breast cancer diagnosis and management. There are, however, questions with regards to the reliability and consistency of CTC detection and to the relationship between CTCs and prognosis, which is limiting their clinical utility. There is increasing acceptance that the ability of CTCs to alter from an epithelial to mesenchymal phenotype plays an important role in determining the metastatic potential of these cells. This review examines the phenotypic and genetic variation, which has been reported within CTC populations. Importantly, we discuss how the detection and characterization of CTCs provides additional and often differing information from that obtained from the primary tumor, and how this may be utilized in determining prognosis and treatment options. It has been shown for example that hormone receptor status often differs between the primary tumor and CTCs, which may help to explain failure of endocrine treatment. We examine how CTC status may introduce alternative treatment options and also how they may be used to monitor treatment. Finally, we discuss the most interesting current clinical trials involving CTC analysis and note further research that is required before the breast cancer “liquid biopsy” can be realized

Does paying pay off?

The ongoing degradation of ecosystems threaten future food production and the international community thus urgently has to plan for how to secure fundamental life-support services for the future, so called ecosystem services (ES). Examples of such ES are climate regulation, nutrient cycles, fresh water provision, etc.This report is focused on two distinct strategies to make land users in tropical rainforest areas continue to provide ecosystem services. The first approach, Payment for Ecosystem Services (PES), is an economic instrument designed at global and national levels. Several PES schemes are currently implemented in a global context where increasing human demands for food, fibre and fuel are accelerating competition for land. The overall aim of the PES projects covered by this report is to lower the emission of green house gas on national and global levels and they are especially directed towards forest areas. The PES projects specify that specific rural groups are paid if they agree to protect, manage or restore the ecosystem service provisioning system within their forest territories. This report highlights that many PES initiatives are being implemented with a ‘conservation perspective’, rather than seeing ecosystem services as integrated with production and livelihoods. There are also alternative strategies to manage ecosystem services. In this report we put an emphasis on an approach where production and conservation are planned for within the same landscape and production systems. Many smallholders already integrate and maintain ecosystem services in their agricultural/forest production systems in a long-term perspective, while producing food, fibre and fuel for the households’ own consumption as well as for sale. In such a system, the local communities are totally dependent on the ecosystem services to re-generate conditions for their agricultural production and/or forest extraction. The focus in such farming-forestry systems, using little or no inputs, which are totally dependent on renewable resources, is on how to increase agricultural/forest production by supporting local ecosystem services, such as soil fertility and structure, pollination, micro climate, biological control of crop pests, etc. The ecosystem services functions, such as carbon sequestration, then emerge as a ‘by-product’ out of these production systems. Increased soil humus in the soil and biomass accumulation are other examples of such ‘by-products’. We want to illustrate potentials and challenges with the aforementioned two approaches to secure ecosystem provisions, and how they are articulated within their specific contexts. This report explores these two approaches by examining case-studies in tropical forest areas in Peru, Brazil, Tanzania and Vietnam, as well as the experiences of EU-designed PES schemes for subsidies/support so as to achieve environmental protection in Sweden