Protein phosphatase types 1 (PP1) and 2A (PP2A) represent two major families of serine/threonine protein phosphatases that have been implicated in the regulation of many cellular processes, including cell growth and apoptosis in mammalian cells. PP1 and PP2A proteins are composed of oligomeric complexes comprising a catalytic structure (PP1c or PP2AC) containing the enzymatic activity and at least one more interacting subunit. The binding of different subunits to a catalytic structure generates a broad variety of holoenzymes. We showed here that casein kinase 2␣ (Ck2␣) and simian virus 40 small t antigen share a putative common ␤-strand structure required for PP2A1 trimeric holoenzyme binding. We have also characterized DPT-sh1, a short basic peptide from Ck2␣ that interacted only in vitro with the PP2A-A subunit and behaves as a nontoxic penetrating shuttle in several cultivated human cell lines and chick embryos. In addition, DPT-sh1 specifically accumulated in human red cells infected with Plasmodium falciparum malaria parasites. We therefore designed bipartite peptides containing DPT-sh1 and PP1-or PP2A-interacting sequences. We found that DPT-5, a DPT-sh1-derived peptide containing a short sequence identified in CD28 antigen, interacts with PP2A-B␣, and DPT-7, another DPT-sh1-derived peptide containing a short sequence identified in Bad as a PP1 catalytic consensus docking motif, induce apoptosis in cultivated cell lines. These results clearly indicate that the rational design of PP1/PP2A interacting peptides is a pertinent strategy to deregulate intracellular survival pathways.In eukaryotic cells, biological activity of nearly 30% of proteins is modulated by phosphorylation. Reversible protein phosphorylation regulates multiple cellular processes, including metabolism, signal transduction pathways, cell cycle progression, oncogenic transformation, cell differentiation, and apoptosis (Garcia et al., , 2003. Protein phosphorylation regulates the activities of protein kinases and protein phosphatases themselves (Hunter, 2000). Type 1 (PP1) and type 2A (PP2A) Ser/Thr protein phosphatases are major regulators of cell dephosphorylation. Binding of PP1 catalytic subunit (PP1c) to specific regulatory subunits generates a large family of PP1 holoenzymes (Cohen, 2002). For PP2AThis work was supported in part by the Institut-Pasteur (PTR-136 and DVPI 27147-27188) and by the Association pour la Recherche sur le Cancer grant 4437 (to A.G.) and grant 4812 (to S.A.S.). F.D. was supported by a fellowship grant from Institut-Pasteur (DVPI). J.G. is a recipient of a Ministere de la Recherche et Technologie fellowship from the French Government. V.J.Y. was supported by a Marie Curie IntraEuropean fellowship within the 6th European Community Framework Programme (contract MEIF-2003-501887

Linezolid, clarithromycin or moxifloxacin, could be used as alternative drugs for treatment of infections due to rifampicin-resistant isolates as well as short-course or intermittent therapy of M. kansasii lung disease.

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HIV infections are still a very serious concern for public heath worldwide. We have applied molecular evolution methods to study the HIV-1 epidemics in the Comunidad Valenciana (CV, Spain) from a public health surveillance perspective. For this, we analysed 1804 HIV-1 sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2004 and 2014. These sequences were subtyped and subjected to phylogenetic analyses in order to detect transmission clusters. In addition, univariate and multinomial comparisons were performed to detect epidemiological differences between HIV-1 subtypes, and risk groups. The HIV epidemic in the CV is dominated by subtype B infections among local men who have sex with men (MSM). 270 transmission clusters were identified (>57% of the dataset), 12 of which included ≥10 patients; 11 of subtype B (9 affecting MSMs) and one (n = 21) of CRF14, affecting predominately intravenous drug users (IDUs). Dated phylogenies revealed these large clusters to have originated from the mid-80s to the early 00 s. Subtype B is more likely to form transmission clusters than non-B variants and MSMs to cluster than other risk groups. Multinomial analyses revealed an association between non-B variants, which are not established in the local population yet, and different foreign groups.

Introduction: Every year, more than 10 million women are diagnosed worldwide with breast cancer. Breast cancer remains the leading cause of death from malignancy in women. In Mexico about 12 Mexican women die every day from this disease. Glutathione S-transferase (GST) family consists of a group of isoenzymes involved in Phase II detoxification of xenobiotics by glutathione conjugation. There have been reports showing GST polymorphisms as a risk factor for developing cancer. Objective: Determine if the frequencies of polymorphisms of GSTT1, GSTM1 and GSTP1 are associated with breast cancer development. Materials and Methods: We studied 22 women with breast cancer and a control group of 30 women. DNA was extracted from blood. Polymorphisms of T1 and M1 were identified by multiplex PCR. The identification of GSTP1b (exon 5) and GSTP1c (exon 6), was performed separately by RFLP-PCR, using BsmAI and AciI enzymes respectively. Results: Frequencies of polymorphisms were as follows: for breast cancer group 33% null GSTT1 vs 40% null in the control, 32% null GSTM1 vs 63% of control; 63% heterozygote GSTP1b P1a/P1b and 18% homozygote P1b/P1b, vs 53% heterozygote and 20% homozygote in the control, 41% heterozygote P1a/P1c GSTP1c and 0% homozygote vs 10% heterozygote P1c/P1c and 0% homozygote control. Significant differences were found between GSTM1 and GSTP1c polymorphisms with GSTM1 null percentage higher in the control group and a higher frequency of P1c heterozygotes in the cancer group. Conclusion: As this is a pilot study where the results showed no association with breast cancer, further investigation is required on the involvement of GST genes in neoplasm development.