Interplay of Mre11 Nuclease with Dna2 plus Sgs1 in Rad51-Dependent Recombinational Repair

The Mre11/Rad50/Xrs2 complex initiates IR repair by binding to the end of a double-strand break, resulting in 5′ to 3′ exonuclease degradation creating a single-stranded 3′ overhang competent for strand invasion into the unbroken chromosome. The nuclease(s) involved are not well understood. Mre11 encodes a nuclease, but it has 3′ to 5′, rather than 5′ to 3′ activity. Furthermore, mutations that inactivate only the nuclease activity of Mre11 but not its other repair functions, mre11-D56N and mre11-H125N, are resistant to IR. This suggests that another nuclease can catalyze 5′ to 3′ degradation. One candidate nuclease that has not been tested to date because it is encoded by an essential gene is the Dna2 helicase/nuclease. We recently reported the ability to suppress the lethality of a dna2Δ with a pif1Δ. The dna2Δ pif1Δ mutant is IR-resistant. We have determined that dna2Δ pif1Δ mre11-D56N and dna2Δ pif1Δ mre11-H125N strains are equally as sensitive to IR as mre11Δ strains, suggesting that in the absence of Dna2, Mre11 nuclease carries out repair. The dna2Δ pif1Δ mre11-D56N triple mutant is complemented by plasmids expressing Mre11, Dna2 or dna2K1080E, a mutant with defective helicase and functional nuclease, demonstrating that the nuclease of Dna2 compensates for the absence of Mre11 nuclease in IR repair, presumably in 5′ to 3′ degradation at DSB ends. We further show that sgs1Δ mre11-H125N, but not sgs1Δ, is very sensitive to IR, implicating the Sgs1 helicase in the Dna2-mediated pathway

REMOVED: Multicomponent Gas and Vapour Sorption in High Free Volume Polymers

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Association of Previous Measles Infection With Markers of Acute Infectious Disease Among 9- to 59-Month-Old Children in the Democratic Republic of the Congo.

BackgroundTransient immunosuppression and increased susceptibility to other infections after measles infection is well known, but recent studies have suggested the occurrence of an "immune amnesia" that could have long-term immunosuppressive effects.MethodsWe examined the association between past measles infection and acute episodes of fever, cough, and diarrhea among 2350 children aged 9 to 59 months whose mothers were selected for interview in the 2013-2014 Democratic Republic of the Congo (DRC) Demographic and Health Survey (DHS). Classification of children who had had measles was completed using maternal recall and measles immunoglobulin G serostatus obtained via dried-blood-spot analysis with a multiplex immunoassay. The association with time since measles infection and fever, cough, and diarrhea outcomes was also examined.ResultsThe odds of fever in the previous 2 weeks were 1.80 (95% confidence interval [CI], 1.25-2.60) among children for whom measles was reported compared to children with no history of measles. Measles vaccination demonstrated a protective association against selected clinical markers of acute infectious diseases.ConclusionOur results suggest that measles might have a long-term effect on selected clinical markers of acute infectious diseases among children aged 9 to 59 months in the DRC. These findings support the immune-amnesia hypothesis suggested by others and underscore the need for continued evaluation and improvement of the DRC's measles vaccination program

The New Deal: jeopardised by the geography of unemployment?

The New Deal is the Labour government's flagship programme to "end the tragic waste of youth and long-term unemployment" by getting people off welfare benefits and into work. This paper argues that the principal weakness of the New Deal is that it seeks to influence the character of labour supply (i.e. the motivation and skills of the unemployed) while neglecting the state of labour demand, which varies greatly between places. The uneven geography of unemployment in the UK is likely to have a crucial bearing on the programme's impact and effectiveness, but this has been largely ignored in its development. The paper outlines some of the practical consequences of this imbalance and suggests how it could be rectified for the programme to be more effective

Taking connected mobile-health diagnostics of infectious diseases to the field.

Mobile Health or mHealth - The application of mobile devices, their components and related technologies to healthcare is improving patients’ access to treatment and advice. Now, in combination with connected diagnostic devices it offers new possibilities to diagnose, track and control infectious diseases and improve health system efficiencies. In this context we look at these technologies and highlight their promise but also the challenges in realising their potential to increase patient access to testing, aid in their treatment and improve the capability of public health authorities to monitor outbreaks, implement responses, and assess the impact of interventions across the world

New Measurements of Nucleon Structure Functions from the CCFR/NuTeV Collaboration

We report on the extraction of the structure functions F_2 and Delta xF_3 = xF_3nu-xF_3nubar from CCFR neutrino-Fe and antineutrino-Fe differential cross sections. The extraction is performed in a physics model independent (PMI) way. This first measurement for Delta xF_3, which is useful in testing models of heavy charm production, is higher than current theoretical predictions. The F_2 (PMI) values measured in neutrino and muon scattering are in good agreement with the predictions of Next to Leading Order PDFs (using massive charm production schemes), thus resolving the long-standing discrepancy between the two sets of data.Comment: 5 pages. Presented by Arie Bodek at the CIPNAP2000 Conference, Quebec City, May 200