Metabolism of nitro drugs metronidazole and nitazoxanide in Giardia lamblia: characterization of a novel nitroreductase (GlNR2)

Objectives The protozoan parasite Giardia lamblia causes giardiasis, a persistent diarrhoea. Nitro drugs such as the nitroimidazole metronidazole and the nitrothiazolide nitazoxanide are used for the treatment of giardiasis. Nitroreductases may play a role in activating these drugs. G. lamblia contains two nitroreductases, GlNR1 and GlNR2. The aim of this work was to elucidate the role of GlNR2. Methods Expression of GlNR2 was analysed by reverse transcription PCR. Recombinant GlNR2 was overexpressed in G. lamblia and drug susceptibility was analysed. Recombinant GlNR2 was subjected to functional assays. Escherichia coli expressing full-length or truncated GlNR1 and GlNR2 were grown in the presence of nitro compounds. Using E. coli reporter strains for nitric oxide and DNA damage responses, we analysed whether GlNR1 and GlNR2 elicited the respective responses in the presence, or absence, of the drugs. Results G. lamblia trophozoites overexpressing GlNR2 were less susceptible to both nitro drugs as compared with control trophozoites. GlNR2 was a functional nitroreductase when expressed in E. coli. E. coli expressing GlNR1 was more susceptible to metronidazole under aerobic and semi-aerobic and to nitazoxanide under semi-aerobic growth conditions. E. coli expressing GlNR2 was not susceptible to either drug. In reporter strains, GlNR1, but not GlNR2, elicited nitric oxide and DNA repair responses, even in the absence of nitro drugs. Conclusions These findings suggest that GlNR2 is an active nitroreductase with a mode of action different from that of GlNR1. Thus, susceptibility to nitro drugs may depend not only on activation, but also on inactivation of the drugs by specific nitroreductase

Quantifying the Impact of Women’s Participation in Post-Conflict Economic Recovery

There is still a considerable lack of systematic and rigorous understanding about the impact of violent conflict on women‘s roles, activities and aspirations, or about the nature and magnitude of the benefits of including women more fully in economic recovery and peace-building processes. Policy programming around gender issues in post-conflict contexts is currently being designed based on limited rigorous evidence, and incorporates inadequate procedures to evaluate its impact in terms of gender roles and gender equality. This situation has at times resulted in misplaced interventions and the continued emphasis on the reintegration of (male) combatants, and male employment generation programmes. The main aim of this report is to analyse how changes in the roles and activities of women during episodes of violent conflict may shape their contribution to post-conflict economic recovery and sustainable peace. The report poses two important questions for which limited evidence is to date available in the academic literature on violent conflict or in policy programming in post-conflict contexts: 1) How does violent conflict change the roles that women take on within their households and communities? 2) How do changes in female roles during conflict affect women‘s own status after the conflict, and the capacity of households and communities to recover from the conflict?UN Wome

Hair concentrations of anti-malarials in returned travellers-the HAIR study: Proof of principle analysis

Background: Hair analysis to identify substance use is an established methodology. This could also be a method to monitor adherence to antimalarial drugs. We aimed to establish a methodology to determine hair concentrations of atovaquone, proguanil and mefloquine in travellers using chemoprophylaxis. Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous analysis of the antimalarial drugs -atovaquone (ATQ), proguanil (PRO) and mefloquine (MQ), in human hair. The hair samples from five volunteers were used for this proof-of-concept analysis. Three volunteers were taking daily atovaquone/proguanil (ATQ/PRO) chemoprophylaxis and two volunteers were using weekly mefloquine (MQ) chemoprophylaxis. Results: With this proof-of-principle analysis, we could show that ATQ/PRO and MQ are integrated into the hair matrix. Chemoprophylaxis could be quantified with the established method. In hair segments, maximal concentrations of 3.0 ng/mL/20 mg hair proguanil, 1.3 ng/mL/20 mg hair atovaquone and 78.3 ng/mL/20 mg hair mefloquine were measured. Moreover, malaria drug concentration changes correlated with the time interval since finishing the chemoprophylaxis regimen. Conclusions: The validated method was used successfully for the analysis of antimalarial-drug positive hair samples containing atovaquone, proguanil or mefloquine. This research shows that hair can be used for adherence monitoring of chemoprophylaxis and paves the way for larger studies and optimized procedures

Higher Twist Distribution Amplitudes of Vector Mesons in QCD: Twist-4 Distributions and Meson Mass Corrections

We present a systematic study of twist-4 light-cone distribution amplitudes of vector mesons in QCD, which is based on conformal expansion. The structure of meson mass corrections is studied in detail. A complete set of distribution amplitudes is constructed, which satisfies all (exact) equations of motion and constraints from conformal expansion. Nonperturbative input parameters are estimated from QCD sum rules. Our study suggests that meson mass corrections may present a dominant source of higher twist effects in exclusive processes.Comment: 38 pages Latex, 2 postscript figure

The Origin of Citizen Genet’s Projected Attack on Spanish Louisiana: A Case Study in Girondin Politics

In 1792 the Girondin ministry decided to send Edmond Genet to the United States with plans to recruit western frontiersmen and invade Spanish Louisiana. The episode is well known in American history, but the literature on its French origin is sparse and overemphasizes the contribution of revolutionary leader Jacques- Pierre Brissot. This essay contextualizes the French decision within the debate between Brissot, Minister of Foreign Affairs Pierre Lebrun, and General Charles-François Dumouriez over whether France should send troops against Spanish colonies in South America. The essay argues that Lebrun promoted the western scheme in order to attack Spanish interests without straining French resources. Rather than merely embodying a spirit of universal freedom, Lebrun’s plan was grounded in the geopolitical advantages the mission might afford France in its European wars

How does learners’ behavior attract preservice teachers’ attention during teaching?

Teachers need to continuously monitor students’ engagement in classrooms, but novice teachers have difficulties paying attention to individual behavioral cues in all learners. To investigate these interaction processes in more detail, we re-analyzed eye-tracking data from preservice teachers teaching simulated learners who engaged in different behaviors (Stürmer, Seidel, Müller, Häusler, & Cortina, 2017). With a new methodological approach, we synchronized the data with a continuous annotation of observable student behavior and conducted time series analysis on 3646 s of video material. Results indicate that novice teachers’ attention is attracted most often when learners show (inter)active learning-related behavior

The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis

The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage

Comment on “Nature and entropy content of the ordering transitions in RCo₂”

In their analysis of our perturbed angular correlation (PAC) study of the magnetic phase transitions of RCo₂ [Phys. Rev. B 68, 014409 (2003)], Herrero-Albillos [Phys. Rev. B 73, 134410 (2006)] come to the conclusion that it is very difficult for PAC spectroscopy to distinguish a first-order from a second-order phase transition. The statement is incorrect and does not resolve the conflict between the conclusion drawn from the PAC data and the differential scanning calorimetry data of Herrero- Albillos on the order of the magnetic phase transitions of PrCo₂ and NdCo₂. In this Comment we show that measurements of hyperfine interactions by PAC and other microscopic techniques are a very powerful tool for the investigation of phase transitions which may provide details on the transition not accessible to macroscopic methods. We explain why the PAC data leave no alternative to the conclusion that the spontaneous magnetization of PrCo₂ and NdCo₂ undergoes a discontinuous, first-order phase transition at T_(C)