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Cell cycle progression and cell division are driven by the sequential activation of a group of serine-threonine kinases called cyclin-dependent kinases (Cdks). Multiple Cdks control the cell cycle in mammals and have been long considered essential for normal proliferation, development and homeostasis. The importance of the Cdk-cyclin complexes in cell proliferation is underscored by the fact that deregulation of the Cdk activity is found in virtually the whole spectrum of human tumors. Advances in the cell cycle proteins in the last 25 years, since the discovery of cyclins, have been discussed and have shed even more light on this essential life sustaining process. Recent information from different models for the various cyclins and Cdks have made some of the generally accepted concepts of cell cycle regulation to be revised and new and exciting questions to be investigated. There is also increasing evidence that suggests that Cdks such as Cdc2 are also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. This review, describes some of the most recent and important US patents related to cell cycle regulation and those on viral proteins involved in cell cycle modulation particularly the G2/M phase transition and cancer therapy.

, p53, p21 cip1/waf1 , Cdc2, cyclin B1, Chk1, Chk2, and Cdc25C, suggesting that p17 induces a G 2 /M cell cycle arrest through activation of the ATM/p53/p21 cip1/waf1 /Cdc2/cyclin B1 and ATM/Chk1/Chk2/Cdc25C pathways. The G 2 /M cell cycle arrest resulted in increased virus replication. In the present study, we also provide evidence demonstrating that p17 protein is responsible for ARV-induced host cellular protein translation shutoff. Increased phosphorylation levels of the eukaryotic translation elongation factor 2 (eEF2) and initiation factor eIF2␣ and reduced phosphorylation levels of the eukaryotic translation initiation factors eIF4E, eIF4B, and eIF4G, as well as 4E-BP1 and Mnk-1 in p17-transfected cells, demonstrated that ARV p17 suppresses translation initiation factors and translation elongation factors to induce host cellular protein translation shutoff. Inhibition of mTOR by rapamycin resulted in a decrease in the levels of phosphorylated 4E-BP1, eIF4B, and eIF4G and an increase in the levels eEF2 but did not affect ARV replication, suggesting that ARV replication was not hindered by inhibition of cap-dependent translation. Taken together, our data indicate that ARV p17-induced G 2 /M arrest and host cellular translation shutoff resulted in increased ARV replication.

Rabies is a devastating zoonotic disease causing nearly 60,000 deaths globally each year. The disease causes Malawi an economic loss of 13 million USD and kills almost 500 people annually. Domestic dogs are the main reservoir for rabies and vaccinating over 70% of the dog population is the most efficient method to reduce its incidence in both humans and canines. However, achieving such coverages is often difficult and depend on many geospatial factors. Rural and pastoral regions are considered difficult to vaccinate efficiently due to low dog densities, and reports of campaigns spanning large areas containing vastly different communities are lacking. This study describes a mass canine vaccination campaign covering rural and urban regions in southern Malawi. The campaign achieved an average vaccination coverage of 83.4% across 3 districts, and vaccinated over 89,000 dogs through a combined static point and door-to-door effort. A dog population of 107,574 dogs was estimated (dog:human ratio of 1:23). The canine population was found to be almost completely owned (99.2%) and mostly kept for security purposes (82.7%). The dogs were mainly adults, males, and not neutered. Regression analysis identified education level and proportion of young dogs as the only factors influencing (positively and negatively, respectively) whether vaccination coverage over 70% was achieved in a region, independently of variables such as population density or poverty. A second regression analysis was performed predicting absolute vaccination coverage. While education level and the proportion of confined dogs were associated with positive vaccination coverage, higher proportions of young animals and female dogs were associated with a decrease in coverage. This study confirms the feasibility of homogeneously vaccinating over 70% of the dogs in a large area including rural and urban communities. These findings can inform the logistics of future campaigns and might be used as a template to facilitate high-number, high-coverage vaccination campaigns to other regions in sub-Saharan Africa.