Pan-eukaryote ITS2 homologies revealed by RNA secondary structure

For evolutionary comparisons, phylogenetics and evaluation of potential interbreeding taxa of a species, various loci have served for animals and plants and protistans. One [second internal transcribed spacer (ITS2) of the nuclear ribosomal DNA] is highly suitable for all. Its sequence is species specific. It has already been used extensively and very successfully for plants and some protistans, and a few animals (where historically, the mitochondrial genes have dominated species studies). Despite initial impressions that ITS2 is too variable, it has proven to provide useful biological information at higher taxonomic levels, even across all eukaryotes, thanks to the conserved aspects of its transcript secondary structure. The review of all eukaryote groups reveals that ITS2 is expandable, but always retains in its RNA transcript a common core structure of two helices with hallmark characteristics important for ribosomal RNA processing. This aspect of its RNA transcript secondary structure can rescue difficult alignment problems, making the ITS2 a more powerful tool for phylogenetics. Equally important, the recognition of eukaryote-wide homology regions provides extensive and detailed information to test experimental studies of ribosomal rRNA processing

A Quantitative Study of Dropout and Suspension Rates of Native American High School Students Enrolled in Title VII and Non-Title VII School Districts

The North Carolina Commission of Indian Affairs (NCCIA) works collaboratively with The North Carolina State Advisory Council on Indian Education (SACIE) to support educational agencies with large populations of American Indian and Alaska Native students. The North Carolina Department of Public Instruction (NCDPI) and the North Carolina SACIE identified the American Indian students as having one of the highest dropout rates in North Carolina. This quantitative study employed a design combining causal comparative and correlational methods to examine the relationship between high school dropout and suspension rates among American Indian high school students enrolled in school districts that provide Title VII Indian Education Programs and school districts that do not provide Title VII Indian Education Programs. The findings of the study indicated that there was a significant effect of the Title VII Indian Education Program on high school male and female Native American engagement as evident by lower student dropout rates. There was no effect on student participation on long or short term suspension rates, however, there was a relationship between the student suspension rates and dropout rates of the study participants

Anidulafungin compared with fluconazole for treatment of candidemia and other forms of invasive candidiasis caused by Candida albicans: a multivariate analysis of factors associated with improved outcome

<p>Abstract</p> <p>Background</p> <p><it>Candida albicans </it>is the most common cause of candidemia and other forms of invasive candidiasis. Systemic infections due to <it>C. albicans </it>exhibit good susceptibility to fluconazole and echinocandins. However, the echinocandin anidulafungin was recently demonstrated to be more effective than fluconazole for systemic <it>Candida </it>infections in a randomized, double-blind trial among 245 patients. In that trial, most infections were caused by <it>C. albicans</it>, and all respective isolates were susceptible to randomized study drug. We sought to better understand the factors associated with the enhanced efficacy of anidulafungin and hypothesized that intrinsic properties of the antifungal agents contributed to the treatment differences.</p> <p>Methods</p> <p>Global responses at end of intravenous study treatment in patients with <it>C. albicans </it>infection were compared post-hoc. Multivariate logistic regression analyses were performed to predict response and to adjust for differences in independent baseline characteristics. Analyses focused on time to negative blood cultures, persistent infection at end of intravenous study treatment, and 6-week survival.</p> <p>Results</p> <p>In total, 135 patients with <it>C. albicans </it>infections were identified. Among these, baseline APACHE II scores were similar between treatment arms. In these patients, global response was significantly better for anidulafungin than fluconazole (81.1% vs 62.3%; 95% confidence interval [CI] for difference, 3.7-33.9). After adjusting for baseline characteristics, the odds ratio for global response was 2.36 (95% CI, 1.06-5.25). Study treatment and APACHE II score were significant predictors of outcome. The most predictive logistic regression model found that the odds ratio for study treatment was 2.60 (95% CI, 1.14-5.91) in favor of anidulafungin, and the odds ratio for APACHE II score was 0.935 (95% CI, 0.885-0.987), with poorer responses associated with higher baseline APACHE II scores. Anidulafungin was associated with significantly faster clearance of blood cultures (log-rank <it>p </it>< 0.05) and significantly fewer persistent infections (2.7% vs 13.1%; <it>p </it>< 0.05). Survival through 6 weeks did not differ between treatment groups.</p> <p>Conclusions</p> <p>In patients with <it>C. albicans </it>infection, anidulafungin was more effective than fluconazole, with more rapid clearance of positive blood cultures. This suggests that the fungicidal activity of echinocandins may have important clinical implications.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00058682">NCT00058682</a></p

Culturing of the first 37:4 predominant lacustrine haptophyte : geochemical, biochemical, and genetic implications

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 78 (2012): 51–64, doi:10.1016/j.gca.2011.11.024.Long chain alkenones (LCAs) are potential biomarkers for quantitative paleotemperature reconstructions from lacustrine environments. However, progress in this area has been severely hindered by the lack of culture studies of haptophytes responsible for alkenone distributions in lake sediments: the predominance of C37:4 LCA. Here we report the first enrichment culturing of a novel haptophyte phylotype (Hap-A) from Lake George, ND that produces predominantly C37:4-LCA. Hap-A was enriched from its resting phase collected from deep sediments rather than from water column samples. In contrast, enrichments from near surface water yielded a different haptophyte phylotype (Hap-B), closely related to Chrysotila lamellosa and Pseudoisochrysis paradoxa, which does not display C37:4-LCA predominance (similar enrichments have been reported previously). The LCA profile in sediments resembles that of Hap-A enrichments, suggesting that Hap-A is the dominant alkenone producer of the sedimentary LCAs. In enrichments, excess lighting appeared to be crucial for triggering blooms of Hap-A. Both and indices show a linear relationship with temperature for Hap-A in enrichments, but the relationship appears to be dependent on the growth stage. Based on 18S rRNA gene analyses, several lakes from the Northern Great Plains, as well as Pyramid Lake, NV and Tso Ur, Tibetan Plateau, China contain the same two haptophyte phylotypes. The Great Plains lakes show the Hap-A-type LCA distribution, whereas Pyramid and Tso Ur show the Hap-B type distribution. Waters of the Great Plain lakes are dominated by sulfate, whereas those Pyramid and Tso Ur are dominated by carbonate, suggesting that the sulfate to carbonate ratio may be a determining factor for the competitiveness of the Hap-A and Hap-B phylotypes in natural settings.This work was supported by a grant from the National Science Foundation to Y. Huang (EAR06-02325) and a Brown University Graduate School Dissertation Fellowship to J. L. Toney

Associations of risk factors of e-cigarette and cigarette use and susceptibility to use among baseline PATH study youth participants (2013–2014)

Introduction: Improved understanding of the distribution of traditional risk factors of cigarette smoking among youth who have ever used or are susceptible to e-cigarettes and cigarettes will inform future longitudinal studies examining transitions in use. Methods: Multiple logistic regression analysis was conducted using data from youth (ages 12–17 years) who had ever heard of e-cigarettes at baseline of the PATH Study (n = 12,460) to compare the distribution of risk factors for cigarette smoking among seven mutually exclusive groups based on ever cigarette/e-cigarette use and sus- ceptibility status. Results: Compared to committed never users, youth susceptible to e-cigarettes, cigarettes, or both had increasing odds of risk factors for cigarette smoking, with those susceptible to both products at highest risk, followed by cigarettes and e-cigarettes. Compared to e-cigarette only users, dual users had higher odds of nearly all risk factors (aOR range = 1.6–6.8) and cigarette only smokers had higher odds of other (non-e-cigarette) tobacco use (aOR range=1.5–2.3), marijuana use (aOR=1.9, 95%CI=1.4–2.5), a high GAIN substance use score (aOR = 1.9, 95%CI = 1.1–3.4), low academic achievement (aOR range = 1.6–3.4), and exposure to smoking (aOR range = 1.8–2.1). No differences were observed for externalizing factors (depression, anxiety, etc.), sen- sation seeking, or household use of non-cigarette tobacco. Conclusions: Among ever cigarette and e-cigarette users, dual users had higher odds of reporting traditional risk factors for smoking, followed by single product cigarette smokers and e-cigarette users. Understanding how e- cigarette and cigarette users differ may inform youth tobacco use prevention efforts and advise future studies assessing probability of progression of cigarette and e-cigarette use

Conducting Health Research in Korean American Churches: Perspectives from Church Leaders

Korean Americans experience many challenges to obtaining adequate health care coverage and access to needed services. Because a large proportion of Korean Americans attend churches on a regular basis, churches may be a promising venue where health programs can be delivered. In order to gain an in-depth understanding of Korean American churches with respect to conducting future health intervention research, we conducted exploratory interviews and focus groups with 58 leaders from 23 Korean American churches and three community organizations. From these interviews and focus groups, we found that Korean churches and church leaders seek to meet a variety of social and health needs of their congregation and their surrounding community. Several leaders have stated that assisting with social and medical needs of their members is an important component of their current ministry. They described profound health needs of their congregations and have suggested various ways in which the university can partner with the local churches to help address these needs through research. Additionally, they described various resources churches can provide to researchers such as: their personal assistance, church volunteer base, church facility, and church network and contacts. Our findings suggest that Korean churches have a high potential to serve an important role in the health of Korean Americans. On the basis of the promising results of the present study, we are planning to conduct a cross sectional survey of Korean church leaders and members in Los Angeles County to substantiate our findings in a larger representative sample

Transmission blocking activity of a standardized neem (Azadirachta indica) seed extract on the rodent malaria parasite Plasmodium berghei in its vector Anopheles stephensi

<p>Abstract</p> <p>Background</p> <p>The wide use of gametocytocidal artemisinin-based combination therapy (ACT) lead to a reduction of <it>Plasmodium falciparum </it>transmission in several African endemic settings. An increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on <it>Plasmodium </it>stages developing in the vector. Azadirachtin, a limonoid (tetranortriterpenoid) abundant in neem (<it>Azadirachta indica</it>, Meliaceae) seeds, is a promising candidate, inhibiting <it>Plasmodium </it>exflagellation <it>in vitro </it>at low concentrations. This work aimed at assessing the transmission-blocking potential of NeemAzal^®, an azadirachtin-enriched extract of neem seeds, using the rodent malaria <it>in vivo </it>model <it>Plasmodium berghei</it>/<it>Anopheles stephensi</it>.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>females were offered a blood-meal on <it>P. berghei </it>infected, gametocytaemic BALB/c mice, treated intraperitoneally with NeemAzal, one hour before feeding. The transmission-blocking activity of the product was evaluated by assessing oocyst prevalence, oocyst density and capacity to infect healthy mice. To characterize the anti-plasmodial effects of NeemAzal^®on early midgut stages, i.e. zygotes and ookinetes, Giemsa-stained mosquito midgut smears were examined.</p> <p>Results</p> <p>NeemAzal^®completely blocked <it>P. berghei </it>development in the vector, at an azadirachtin dose of 50 mg/kg mouse body weight. The totally 138 examined, treated mosquitoes (three experimental replications) did not reveal any oocyst and none of the healthy mice exposed to their bites developed parasitaemia. The examination of midgut content smears revealed a reduced number of zygotes and post-zygotic forms and the absence of mature ookinetes in treated mosquitoes. Post-zygotic forms showed several morphological alterations, compatible with the hypothesis of an azadirachtin interference with the functionality of the microtubule organizing centres and with the assembly of cytoskeletal microtubules, which are both fundamental processes in <it>Plasmodium </it>gametogenesis and ookinete formation.</p> <p>Conclusions</p> <p>This work demonstrated <it>in vivo </it>transmission blocking activity of an azadirachtin-enriched neem seed extract at an azadirachtin dose compatible with 'druggability' requisites. These results and evidence of anti-plasmodial activity of neem products accumulated over the last years encourage to convey neem compounds into the drug discovery & development pipeline and to evaluate their potential for the design of novel or improved transmission-blocking remedies.</p

Exposure to Apoptotic Activated CD4+ T Cells Induces Maturation and APOBEC3G- Mediated Inhibition of HIV-1 Infection in Dendritic Cells

Dendritic cells (DCs) are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4+ T cells (ApoInf) or apoptotic uninfected activated CD4+ T cells (ApoAct) induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4+ T cells (ApoRest). Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection

Toward interoperable bioscience data

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Genetics 44 (2012): 121-126, doi:10.1038/ng.1054.To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.The authors also acknowledge the following funding sources in particular: UK Biotechnology and Biological Sciences Research Council (BBSRC) BB/I000771/1 to S.-A.S. and A.T.; UK BBSRC BB/I025840/1 to S.-A.S.; UK BBSRC BB/I000917/1 to D.F.; EU CarcinoGENOMICS (PL037712) to J.K.; US National Institutes of Health (NIH) 1RC2CA148222-01 to W.H. and the HSCI; US MIRADA LTERS DEB-0717390 and Alfred P. Sloan Foundation (ICoMM) to L.A.-Z.; Swiss Federal Government through the Federal Office of Education and Science (FOES) to L.B. and I.X.; EU Innovative Medicines Initiative (IMI) Open PHACTS 115191 to C.T.E.; US Department of Energy (DOE) DE-AC02- 06CH11357 and Arthur P. Sloan Foundation (2011- 6-05) to J.G.; UK BBSRC SysMO-DB2 BB/I004637/1 and BBG0102181 to C.G.; UK BBSRC BB/I000933/1 to C.S. and J.L.G.; UK MRC UD99999906 to J.L.G.; US NIH R21 MH087336 (National Institute of Mental Health) and R00 GM079953 (National Institute of General Medical Science) to A.L.; NIH U54 HG006097 to J.C. and C.E.S.; Australian government through the National Collaborative Research Infrastructure Strategy (NCRIS); BIRN U24-RR025736 and BioScholar RO1-GM083871 to G.B. and the 2009 Super Science initiative to C.A.S