In vitro transposition of ISY100, a bacterial insertion sequence belonging to the Tc1/mariner family

The Synechocystis sp. PCC6803 insertion sequence ISY100 (ISTcSa) belongs to the Tc1/mariner/IS630 family of transposable elements. ISY100 transposase was purified and shown to promote transposition in vitro. Transposase binds specifically to ISY100 terminal inverted repeat sequences via an N-terminal DNA-binding domain containing two helix–turn–helix motifs. Transposase is the only protein required for excision and integration of ISY100. Transposase made double-strand breaks on a supercoiled DNA molecule containing a mini-ISY100 transposon, cleaving exactly at the transposon 3′ ends and two nucleotides inside the 5′ ends. Cleavage of short linear substrates containing a single transposon end was less precise. Transposase also catalysed strand transfer, covalently joining the transposon 3′ end to the target DNA. When a donor plasmid carrying a mini-ISY100 was incubated with a target plasmid and transposase, the most common products were insertions of one transposon end into the target DNA, but insertions of both ends at a single target site could be recovered after transformation into Escherichia coli. Insertions were almost exclusively into TA dinucleotides, and the target TA was duplicated on insertion. Our results demonstrate that there are no fundamental differences between the transposition mechanisms of IS630 family elements in bacteria and Tc1/mariner elements in higher eukaryotes

Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women

PURPOSE: Mammographic breast and bone mineral densities (BMD) have been associated with luteal phase hormone concentrations in premenopausal women. We assessed the associations of breast and bone densities with follicular phase hormones and sex hormone binding globulin (SHBG) in premenopausal women given that follicular phase hormones have been shown to be positively associated with premenopausal breast cancer risk. METHODS: One hundred and ninety two 40-45 year old women provided a spot urine and/or blood sample during the follicular phase. Hormone and SHBG concentrations and bone density were measured and routine mammograms were accessed and digitized to obtain breast density measures. Regression models were fit to assess the associations between hormones and SHBG and breast and bone densities. RESULTS: Positive associations were observed between percent breast density and SHBG (p trend = 0.02), as well as estradiol (p trend = 0.08), after controlling for body mass index (BMI), number of pregnancies, and breast feeding history. In addition, a statistically significant inverse association was observed between total testosterone and head BMD (p trend = 0.01), after controlling for BMI. CONCLUSIONS: Associations were observed between breast and bone densities and serum hormone concentrations during the follicular phase of the menstrual cycle

One-loop N-point equivalence among negative-dimensional, Mellin-Barnes and Feynman parametrization approaches to Feynman integrals

We show that at one-loop order, negative-dimensional, Mellin-Barnes' (MB) and Feynman parametrization (FP) approaches to Feynman loop integrals calculations are equivalent. Starting with a generating functional, for two and then for $N$-point scalar integrals we show how to reobtain MB results, using negative-dimensional and FP techniques. The $N-$point result is valid for different masses, arbitrary exponents of propagators and dimension.Comment: 11 pages, LaTeX. To be published in J.Phys.

Iron and vitamin interactions in marine diatom isolates and natural assemblages of the Northeast Pacific Ocean

Trace metals and B-vitamins play critical roles in regulating marine phytoplankton growth and composition. While some microorganisms are capable of producing certain B-vitamins, others cannot synthesize them and depend on an exogenous supply. Therefore, external factors influencing vitamin synthesis, such as micronutrient concentrations, alter the extent to which B-vitamins are available to auxotrophs in surface waters. We examined iron, B7 (biotin) and B12 (cobalamin) dynamics in diatoms through laboratory culture experiments and within natural diatom assemblages present along an iron gradient in the Northeast Pacific Ocean. In laboratory cultures of the diatom Pseudo-nitzschia granii, biotin synthase (BIOB) expression decreased 2-fold under iron limitation, suggesting iron status may affect B7 production in diatoms. Additionally in laboratory cultures of the diatom Grammonema cf. islandica, which contains a B12-independent methionine synthase (METE), a 15-fold increase in the expression of METE was observed when grown in the absence of B12 with no significant influence of iron status, suggesting METE expression can be driven by B12 status alone. Iron and B-vitamin amendment experiments with natural diatom assemblages in iron-limited waters of the Northeast Pacific Ocean provide evidence for vitamin-associated molecular responses that suggest elevated B7 biosynthesis and the emergence of B12 limitation following iron addition. Furthermore B-vitamin gene modules comprised of partial and/or complete B-vitamin biosynthetic pathways in diatoms increased in response to iron addition, including genes potentially involved in the processing of B12 intermediates. Our results indicate that vitamins may play an important role in regulating phytoplankton growth and composition in this region, particularly following natural iron addition events

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure

Context Is Everything Sociality and Privacy in Online Social Network Sites

International audienceSocial Network Sites (SNSs) pose many privacy issues. Apart from the fact that privacy in an online social network site may sound like an oxymoron, significant privacy issues are caused by the way social structures are currently handled in SNSs. Conceptually different social groups are generally conflated into the singular notion of 'friend'. This chapter argues that attention should be paid to the social dynamics of SNSs and the way people handle social contexts. It shows that SNS technology can be designed to support audience segregation, which should mitigate at least some of the privacy issues in Social Network Sites

Projected Lifetime Healthcare Costs Associated with HIV Infection.

OBJECTIVE: Estimates of healthcare costs associated with HIV infection would provide valuable insight for evaluating the cost-effectiveness of possible prevention interventions. We evaluate the additional lifetime healthcare cost incurred due to living with HIV. METHODS: We used a stochastic computer simulation model to project the distribution of lifetime outcomes and costs of men-who-have-sex-with-men (MSM) infected with HIV in 2013 aged 30, over 10,000 simulations. We assumed a resource-rich setting with no loss to follow-up, and that standards and costs of healthcare management remain as now. RESULTS: Based on a median (interquartile range) life expectancy of 71.5 (45.0-81.5) years for MSM in such a setting, the estimated mean lifetime cost of treating one person was £ 360,800 ($567,000 or € 480,000). With 3.5$291,000 or € 246,000). The largest proportion (68%) of these costs was attributed to antiretroviral drugs. If patented drugs are replaced by generic versions (at 20% cost of patented prices), estimated mean lifetime costs reduced to £ 179,000 ($281,000 or € 238,000) and £ 101,200 ($ 158,900 or € 134,600) discounted. CONCLUSIONS: If 3,000 MSM had been infected in 2013, then future lifetime costs relating to HIV care is likely to be in excess of £ 1 billion. It is imperative for investment into prevention programmes to be continued or scaled-up in settings with good access to HIV care services. Costs would be reduced considerably with use of generic antiretroviral drugs

The effects of user characteristics on query performance in the presence of information request ambiguity

This paper investigates the effects of personality characteristics on individuals' abilities to compose queries from information requests containing various types of ambiguity. In particular, this research examines the effects of user personality characteristics on query performance in the presence of information requests that contained no extraneous, syntactic, or both extraneous and syntactic ambiguities. The results indicate that personality characteristics significantly affect users' abilities to compose accurate queries. Neuroticism, agreeableness, openness to experience, and conscientiousness significantly affected the number of errors made in the query formulations. Conscientiousness affected the length of time taken to compose the queries and neuroticism affected the confidence users had in the accuracy of their queries. Although several personality dimensions affected query performance, no significant interactions between personality dimensions and ambiguity were detected. Furthermore, both query complexity and information request ambiguity exhibited greater impacts on query performance than personality characteristics. Hence, organizations should attempt to train users to deal with query complexity and information request ambiguity before modifying their training programs for personality characteristics

Higgs production as a probe of anomalous top couplings

The LHC may be currently seeing the first hints of the Higgs boson. The dominant production mode for the Higgs at the LHC involves a top-quark loop. An accurate measurement of Higgs production cross-sections and decay widths can thus be used to obtain limits on anomalous top couplings. We find that such an exercise could potentially yield constraints that are stronger than those derived from low-energy observables as well as direct bounds expected from the top pair-production process.Comment: Version published in JHE