Light Effects in Yeast: Evidence for Participation of Cytochromes in Photoinhibition of Growth and Transport in Saccharomyces cerevisiae Cultured at Low Temperatures

Visible light of moderate intensity inhibits growth, respiration, protein synthesis, and membrane transport in bakers' yeast and has a deleterious effect on membrane integrity. The results of this study indicate that these effects require the presence of cytochromes b and a/a(3). The light sensitivities of growth rate and [(14)C]histidine uptake in wild-type rho(+) Y185 and D225-5A strains of Saccharomyces cerevisiae were compared with those in a variety of mutants lacking cytochrome b or a/a(3) or both; a close correlation was found between the presence of these respiratory pigments and photosensitivity. Thus, strain TL5-3C, a nuclear petite lacking cytochromes b, a, and a(3), was resistant to light; strain GL5-6A, another nuclear petite having reduced amounts of cytochromes a and a(3), was partially resistant; strains MB127-20C and MB1-6C, nuclear petites lacking only cytochrome b, were also only partially resistant to light; whereas mutants containing all three cytochromes but having their respiratory chain either nonfunctional (strain ZK3-6B) or uncoupled (strain 18-27/t12) were fully sensitive to light. Finally, an equal-energy, broad-band action spectrum for the light inhibition of growth and transport indicated that blue light (408 nm) was most effective; these wavelengths correspond to the Soret region of the cytochrome absorption spectrum. The results suggest, therefore, that the yeast cytochromes b, a, and a(3) are the primary photoreceptors for the inhibitory effects of light and, perhaps, for other processes, such as the entrainment of biological rhythms in this species.     

Preliminary observations on predator/prey relationships between chaetognaths and copepods in the Java sea

There is evidence that copepods undertake vertical migrations in shallow waters off the north coast of Java. They aggregate at the surface of the sea at dawn and dusk but sink to deeper levels in the middle of the day. Chaetognaths feed on copepods and tend to occur in areas which are rich in their prey. They do not however follow them on vertical migrations during daylight.     

Assessing Optimal Target Populations for Influenza Vaccination Programmes: An Evidence Synthesis and Modelling Study

Background

Influenza vaccine policies that maximise health benefit through efficient use of limited resources are needed. Generally, influenza vaccination programmes have targeted individuals 65 y and over and those at risk, according to World Health Organization recommendations. We developed methods to synthesise the multiplicity of surveillance datasets in order to evaluate how changing target populations in the seasonal vaccination programme would affect infection rate and mortality.

Methods and Findings

Using a contemporary evidence-synthesis approach, we use virological, clinical, epidemiological, and behavioural data to develop an age- and risk-stratified transmission model that reproduces the strain-specific behaviour of influenza over 14 seasons in England and Wales, having accounted for the vaccination uptake over this period. We estimate the reduction in infections and deaths achieved by the historical programme compared with no vaccination, and the reduction had different policies been in place over the period. We find that the current programme has averted 0.39 (95% credible interval 0.34–0.45) infections per dose of vaccine and 1.74 (1.16–3.02) deaths per 1,000 doses. Targeting transmitters by extending the current programme to 5–16-y-old children would increase the efficiency of the total programme, resulting in an overall reduction of 0.70 (0.52–0.81) infections per dose and 1.95 (1.28–3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk (50–64-y-olds) would prevent only 0.43 (0.35–0.52) infections per dose and 1.77 (1.15–3.14) deaths per 1,000 doses.

Conclusions

This study proposes a framework to integrate influenza surveillance data into transmission models. Application to data from England and Wales confirms the role of children as key infection spreaders. The most efficient use of vaccine to reduce overall influenza morbidity and mortality is thus to target children in addition to older adults. Please see later in the article for the Editors'' Summary     

Identifying Transmission Cycles at the Human-Animal Interface: The Role of Animal Reservoirs in Maintaining Gambiense Human African Trypanosomiasis

Many infections can be transmitted between animals and humans. The epidemiological roles of different species can vary from important reservoirs to dead-end hosts. Here, we present a method to identify transmission cycles in different combinations of species from field data. We used this method to synthesise epidemiological and ecological data from Bipindi, Cameroon, a historical focus of gambiense Human African Trypanosomiasis (HAT, sleeping sickness), a disease that has often been considered to be maintained mainly by humans. We estimated the basic reproduction number of gambiense HAT in Bipindi and evaluated the potential for transmission in the absence of human cases. We found that under the assumption of random mixing between vectors and hosts, gambiense HAT could not be maintained in this focus without the contribution of animals. This result remains robust under extensive sensitivity analysis. When using the distributions of species among habitats to estimate the amount of mixing between those species, we found indications for an independent transmission cycle in wild animals. Stochastic simulation of the system confirmed that unless vectors moved between species very rarely, reintroduction would usually occur shortly after elimination of the infection from human populations. This suggests that elimination strategies may have to be reconsidered as targeting human cases alone would be insufficient for control, and reintroduction from animal reservoirs would remain a threat. Our approach is broadly applicable and could reveal animal reservoirs critical to the control of other infectious diseases.     

The limits of post-national citizenship: European Muslims,human rights and the hijab

Innovative approaches to citizenship emerged in the 1990s. Post-national theory suggested that European minorities no longer needed national citizenship because supra-national political structures such as the European Court of Human Rights (ECtHR) offered them protections. Denationalized citizenship held that universal human rights were now available at the national level too as the Council of Europe's member countries had to incorporate human rights principles within their own jurisdictions. New forms of claims-making among European Muslims were cited as evidence of this trend as religious claims, especially relating to the hijab, began to be made through human rights litigation. This paper demonstrates the limits of post-nationalism through a discussion of the outcomes of such claims. While European Muslims are indeed mobilizing around human rights, there is no evidence – at the level of litigation – that this has helped them to win recognition of their religious or cultural rights. This paper explores the reasons for this.     

Design and synthesis of tricyclic cores for kinase inhibition

Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest.     

Doxorubicin prodrug on the basis of tert-butyl cephalosporanate sulfones

Doxorubicin-cephalosporin prodrug adapted to the development of elastases for the liberation of parent drug was synthesized on the basis of cephalosporanate sulfone esters.