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Additional file 2: Table S2 gives the different parsimonious LGK-974 concentration models, and their estimated parameters, selected by the Akaike criterion (jMODELTEST version 0.1.1, written by Posada [51], available at http://​darwin.​uvigo.​es/​software/​jmodeltest.​html). Tree comparisons We compared the phylogenetic history of aes to the phylogenetic history of the strains, based on the concatenated PXD101 nucleotide sequences of six housekeeping genes (trpA, trpB, pabB, putP, icd and polB) and individual gene sequences, as described elsewhere

[19]. Briefly, each phylogenetic tree T i is firstly transformed into a tree-distance matrix D i , the distance between two strains being the number of branches with positive length connecting them along the tree. The resulting tree distance matrix D i allows the initial tree structure T i to be recovered, independently of branch length. Two tree distance matrices (D i and D j ) (corresponding to two gene trees i and j) can be compared by calculating the Euclidian distance

between Torin 2 them (δ ij ) [52]. A low δ ij value means that the similarity between the two tree distance matrices D i and D j is high, and, consequently, that their tree structures T i and T j are close. As several gene tree structures are compared through this Euclidian distance metric, a new distance matrix Δ can be built with the δ ij elements. This Δ matrix can then be transformed into a “”tree of gene trees”" using a neighbour-joining algorithm [53]. To obtain a support value for each partition of this tree, we applied this same procedure

to 500 bootstrapped sets of data, obtaining 500 Δ matrices and finally, a bootstrapped consensus “”tree of gene Methane monooxygenase trees”". A high bootstrap support value separating two sets of gene trees allows incongruent sets of gene trees to be identified; however, a low bootstrap value suggests that the two sets of trees are not incongruent or that there is insufficient phylogenetic information to reject the hypothesis of incongruence. The “”TreeOfTree”" package is available from the website http://​bioinformatics.​lif.​univ-mrs.​fr. Protein structure modelling and analysis Modelling of the Aes protein structure was based on comparison of the available models from MODBASE [54] with models previously obtained using the Tasser-Lite homology modelling server [55, 56]. Although some differences were observed between the models obtained by these two independent approaches, in particular in the N terminus region, the best models proposed by Tasser-Lite and MODBASE were similar overall. Given that our aim was to determine only the approximate location of the Aes polymorphism within the protein structure, the MODBASE model was used for further analysis. The model was finally tested to ensure that it contains an active site consistent with esterase activity. This was carried out using the 3D MSS-Sites program http://​bioserv.​rpbs.​jussieu.

The gains from the global implementation of polio eradication initiatives

are not only monetary. The GPEI has Selleck GS-9973 trained an enormous cadre of staff who understand basic health care needs and can provide services to people in the poorest areas in the world. Activities undertaken under the auspices of the GPEI have also contributed to the improvement of public health at large and increased the effectiveness of other preventive programs. Polio program staff have supported the surveillance of and response to measles, tetanus, meningitis, yellow fever and cholera. Furthermore, in many countries, the GPEI successfully expanded its delivery model to include the distribution of Vitamin A supplements alongside polio immunizations, estimated to have averted at least 1.1 million Vitamin A deficiency-related deaths from 1988 to 2010 [25]. In 2012, GF120918 concentration the World Health Assembly requested a comprehensive GSK2118436 in vivo polio endgame strategy [26], which culminated in the development of the Polio Eradication and Endgame Strategic Plan 2013–2018 [27]. The Plan is based

on broad consultations with national health authorities, global health initiatives, scientific experts, donor partners and other stakeholders. The Plan has four main objectives: to stop all wild poliovirus transmission by the end of 2014 and new cVDPV outbreaks within 120 days of confirmation of the first case; to strengthen immunization systems, introduce IPV into the routine immunization schedule globally and withdraw the use of oral polio vaccines; certify Chloroambucil all regions of the world polio-free by 2018 and ensure the safe containment of all poliovirus stocks; and to ensure that the world remains permanently polio-free with careful legacy planning as well as planning for the transition of assets and the infrastructure of the polio program to benefit

other development goals and global health interventions. The Plan aims to withdraw the use of the type-2 component of OPV in all routine immunization programs by mid-2016. The importance of withdrawing the type-2 component as quickly as possible was reinforced by the 2012 polio outbreaks caused by circulating type-2 vaccine-derived polioviruses, which left 65 children paralyzed in 7 countries: Afghanistan, Chad, the Democratic Republic of Congo, Kenya, Nigeria, Pakistan and Somalia [28]. As of August 13, 2013, 17 cases of polio due to circulating type-2 vaccine-derived polioviruses were reported in 6 countries: Afghanistan, Cameroon, Chad, Nigeria, Pakistan and Somalia [29]. The withdrawal of the type-2 component of OPV will require the strengthening of immunization systems, the introduction of at least one dose of affordable IPV into the routine immunization schedule globally and then the replacement of tOPV with bOPV. This would pave the way for the eventual withdrawal of bOPV use in 2019–2020.