A Mathematical Model of Mitotic Exit in Budding Yeast: The Role of Polo Kinase

Cell cycle progression in eukaryotes is regulated by periodic activation and inactivation of a family of cyclin–dependent kinases (Cdk's). Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins. Mitotic exit in budding yeast is known to involve the interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A and Cdc14), as well as the action of the anaphase promoting complex (APC) in degrading specific proteins in anaphase and telophase. To understand the intricacies of this mechanism, we propose a mathematical model for the molecular events during mitotic exit in budding yeast. The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains. The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses

Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection

What explains gender inequalities in HIV/AIDS prevalence in sub-Saharan Africa? Evidence from the demographic and health surveys

Abstract Background Women are disproportionally affected by human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa (SSA). The determinants of gender inequality in HIV/AIDS may vary across countries and require country-specific interventions to address them. This study aimed to identify the socio-demographic and behavioral characteristics underlying gender inequalities in HIV/AIDS in 21 SSA countries. Methods We applied an extension of the Blinder-Oaxaca decomposition approach to data from Demographic and Health Surveys and AIDS Indicator Surveys to quantify the differences in HIV/AIDS prevalence between women and men attributable to socio-demographic factors, sexual behaviours, and awareness of HIV/AIDS. We decomposed gender inequalities into two components: the percentage attributable to different levels of the risk factors between women and men (the “composition effect”) and the percentage attributable to risk factors having differential effects on HIV/AIDS prevalence in women and men (the “response effect”). Results Descriptive analyses showed that the difference between women and men in HIV/AIDS prevalence varied from a low of 0.68 % (P = 0.008) in Liberia to a high of 11.5 % (P < 0.001) in Swaziland. The decomposition analysis showed that 84 % (P < 0.001) and 92 % (P < 0.001) of the higher prevalence of HIV/AIDS among women in Uganda and Ghana, respectively, was explained by the different distributions of HIV/AIDS risk factors, particularly age at first sex between women and men. In the majority of countries, however, observed gender inequalities in HIV/AIDS were chiefly explained by differences in the responses to risk factors; the differential effects of age, marital status and occupation on prevalence of HIV/AIDS for women and men were among the significant contributors to this component. In Cameroon, Guinea, Malawi and Swaziland, a combination of the composition and response effects explained gender inequalities in HIV/AIDS prevalence. Conclusions The factors that explain gender inequality in HIV/AIDS in SSA vary by country, suggesting that country-specific interventions are needed. Unmeasured factors also contributed substantially to the difference in HIV/AIDS prevalence between women and men, highlighting the need for further study

Methods of nutrition surveillance in low-income countries

Background In 1974 a joint FAO/UNICEF/WHO Expert Committee met to develop methods for nutrition surveillance. There has been much interest and activity in this topic since then, however there is a lack of guidance for practitioners and confusion exists around the terminology of nutrition surveillance. In this paper we propose a classification of data collection activities, consider the technical issues for each category, and examine the potential applications and challenges related to information and communication technology. Analysis There are three major approaches used to collect primary data for nutrition surveillance: repeated cross-sectional surveys; community-based sentinel monitoring; and the collection of data in schools. There are three major sources of secondary data for surveillance: from feeding centres, health facilities, and community-based data collection, including mass screening for malnutrition in children. Surveillance systems involving repeated surveys are suitable for monitoring and comparing national trends and for planning and policy development. To plan at a local level, surveys at district level or in programme implementation areas are ideal, but given the usually high cost of primary data collection, data obtained from health systems are more appropriate provided they are interpreted with caution and with contextual information. For early warning, data from health systems and sentinel site assessments may be valuable, if consistent in their methods of collection and any systematic bias is deemed to be steady. For evaluation purposes, surveillance systems can only give plausible evidence of whether a programme is effective. However the implementation of programmes can be monitored as long as data are collected on process indicators such as access to, and use of, services. Surveillance systems also have an important role to provide information that can be used for advocacy and for promoting accountability for actions or lack of actions, including service delivery. Conclusion This paper identifies issues that affect the collection of nutrition surveillance data, and proposes definitions of terms to differentiate between diverse sources of data of variable accuracy and validity. Increased interest in nutrition globally has resulted in high level commitments to reduce and prevent undernutrition. This review helps to address the need for accurate and regular data to convert these commitments into practice