The first hydrophobic region of the HPV16 E5 protein determines protein cellular location and facilitates anchorage-independent growth

The human papillomavirus type 16 E5 protein (HPV16 E5) is 83 amino acids in length and contains three well-defined hydrophobic regions. The protein is expressed at very limited amounts in transfected cells and the absence of specific antibodies has strongly hampered functional analyses. To investigate the relationship between structure and function we have synthesized a codon-adapted version of the gene (hE5) and prepared a series of N-terminal and C-terminal deletions. Immunofluorescence analyses show colocaliation of the protein with calnexin, an ER marker, EEA-1, an early endosomes marker, and Lamp-2, a lysosomal marker. No major colocalization was found between hE5 and the Golgi marker 58 K. Whereas deletions at the C-terminal end of the protein do not greatly alter the localisation pattern, deletion of the first hydrophobic region results in loss of colocalisation with the ER, early endosomes and lysosomes. Further, we show that while the complete E5 protein confers to HaCaT cells the property to grow in an anchorage-independent manner, deletion of the first hydrophobic region results in loss of growth in soft agar. We conclude that the first hydrophobic region of the E5 protein largely determines the biological properties of the viral protein

Sound, structure and meaning : The bases of prominence ratings in English, French and Spanish

This study tests the influence of acoustic cues and non-acoustic contextual factors on listeners’ perception of prominence in three languages whose prominence systems differ in the phonological patterning of prominence and in the association of prominence with information structure—English, French and Spanish. Native speakers of each language performed an auditory rating task to mark prominent words in samples of conversational speech under two instructions: with prominence defined in terms of acoustic or meaning-related criteria. Logistic regression models tested the role of task instruction, acoustic cues and non-acoustic contextual factors in predicting binary prominence ratings of individual listeners. In all three languages we find similar effects of prosodic phrase structure and acoustic cues (F0, intensity, phone-rate) on prominence ratings, and differences in the effect of word frequency and instruction. In English, where phrasal prominence is used to convey meaning related to information structure, acoustic and meaning criteria converge on very similar prominence ratings. In French and Spanish, where prominence plays a lesser role in signaling information structure, phrasal prominence is perceived more narrowly on structural and acoustic grounds. Prominence ratings from untrained listeners correspond with ToBI pitch accent labels for each language. Distinctions in ToBI pitch accent status (nuclear, prenuclear, unaccented) are reflected in empirical and model-predicted prominence ratings. In addition, words with a ToBI pitch accent type that is typically associated with contrastive focus are more likely to be rated as prominent in Spanish and English, but no such effect is found for French. These findings are discussed in relation to probabilistic models of prominence production and perception.Peer reviewe

A novel codon insert in protease of clade B HIV type 1.

A novel combination of three codon inserts in the pol coding region of HIV-1 RNA was identified in a highly antiretroviral experienced study subject with HIV-1 infection. A one codon insert was observed in the protease region between codon 40 and 41 simultaneously with a two codon insert present in the reverse transcriptase region at codon 69

Dual-Specificity Phosphatases in Neuroblastoma Cell Growth and Differentiation

Dual-specificity phosphatases (DUSPs) are important regulators of neuronal cell growth and differentiation by targeting proteins essential to neuronal survival in signaling pathways, among which the MAP kinases (MAPKs) stand out. DUSPs include the MAPK phosphatases (MKPs), a family of enzymes that directly dephosphorylate MAPKs, as well as the small-size atypical DUSPs, a group of low molecular-weight enzymes which display more heterogeneous substrate specificity. Neuroblastoma (NB) is a malignancy intimately associated with the course of neuronal and neuroendocrine cell differentiation, and constitutes the source of more common extracranial solid pediatric tumors. Here, we review the current knowledge on the involvement of MKPs and small-size atypical DUSPs in NB cell growth and differentiation, and discuss the potential of DUSPs as predictive biomarkers and therapeutic targets in human NB.This work was partially supported by the grants: BIO13/CI/001/BC from BIOEF (EITB maratoia), Basque Country, Spain; SAF2013-48812-R from the Ministerio de Educacion y Ciencia (to R.P.), and SAF2016-79847-R from the Ministerio de Economia y Competitividad (Spain and Fondo Europeo de Desarrollo Regional) (to R.P. and J.I.L.); and 239813 from the Research Council of Norway (to C.E.N-X.)

Effect of Influenza Vaccination on Viral Replication and Immune Response in Persons Infected with Human Immunodeficiency Virus Receiving Potent Antiretroviral Therapy

Nineteen patients infected with human immunodeficiency virus (HIV) with varying levels of viral suppression achieved with antiretroviral therapy were evaluated to determine whether trivalent influenza vaccine activated HIV replication. Humoral immune responses and CD4+ lymphocyte subsets were compared in 5 HIV-uninfected vaccinated subjects. Transient elevations of plasma HIV RNA levels (76-89 copies/mL) appeared within 2 weeks in 3 of 11 patients with 50 copies/mL. HIV DNA decreased in patients with <400 RNA copies/mL at baseline and showed an HIV RNA increase after vaccination (n = 8) when compared with 8 patients with <50 copies/mL at baseline who lacked viral response to vaccination. Concurrent decreases in proviral DNA and memory phenotype CD4+ cells in association with increased plasma HIV RNA after vaccination in patients with <400 RNA copies/mL at baseline suggest that in vivo mobilization of the latently infected cell reservoir may occur during potent antiretroviral therap

Personal beliefs and social norms regarding the sexual exploitation of girls in age-disparate transactional sexual relationships in Brazil: a mixed-methods study.

BACKGROUND: In the global debate around transactional sex little attention has concentrated on Brazil, despite ranking fourth globally in absolute number of girls married or co-habiting by the age of 15 years, and evidence showing that these unions often begin as age-disparate transactional sex (ADTS). This article contributes to filling this gap by exploring the personal beliefs and social norms related to ADTS in urban (favela) communities of Rio de Janeiro, Brazil between adult men (> 18 years) and girls and adolescents (G/A) (< 18 years) with a minimum 5-year age disparity. The primary objective of this study was to identify the social norms that promote and prevent ADTS, and the dynamics between individual beliefs and social norms, to provide contextualized recommendations to prevent ADTS in this setting. METHODS: An exploratory, sequential, mixed-methods design was used, starting with a qualitative phase that included semi-structured, in-depth interviews and focus groups, and a subsequent quantitative phase comprising of a community survey. The items for the quantitative questionnaires were developed based on the qualitative results. RESULTS: Mixed methods results indicate that in these communities ADTS is normalised and not considered exploitative. We identified three themes related to the reasons ADTS occurs: girls' responsibility, male desires and benefits of ADTS. Men's role in ADTS was largely minimised because of a general acceptance of a notion of masculinity characterised by hypersexuality and lack of impulse control. Individual beliefs, however, did not tend to align with these social norms. CONCLUSIONS: In this study, personal beliefs and social norms often did not align, suggesting that initiatives working to change personal or attitudes regarding ADTS may not lead to meaningful change in ADTS behaviours, and social norms interventions may be more effective. Our findings reinforce the need to develop programs tailored to local understandings of ADTS, targeting not only girls but also a wide range of actors. Interventions could also consider the structural factors acting in local and global contexts that promote or prevent ADTS

Socioenvironmental conditions and intestinal parasitic infections in Brazilian urban slums: a cross-sectional study

Intestinal parasitic infections (IPIs) are neglected diseases with limited data regarding prevalence in Brazil and many other countries. In increasingly urban societies, investigating the profile and socioenvironmental determinants of IPIs in the general population of slum dwellers is necessary for establishing appropriate public policies catered to these environments. This study assessed the socioenvironmental conditions and prevalence of IPIs in slums of Rio de Janeiro, RJ State, Brazil. Methods A cross-sectional study covering an agglomeration of urban slums was conducted between 2015 and 2016 using participants observation, a socioeconomic survey, and the spontaneous sedimentation method with three slides per sample to analyze fresh stool specimens ( n =595) searching for intestinal parasites. Results Endolimax nana ( n =95, 16.0%) and Entamoeba coli ( n =65, 10.9%) were the most frequently identified agents, followed by Giardia intestinalis ( n =24, 4.0%) and Ascaris lumbricoides ( n =11, 1.8%). Coinfections caused by E. nana and E. histolytica/dispar and by Entamoeba coli/A. lumbricoides were significant. The use of piped water as drinking water, the presence of A. lumbricoides , and contamination with coliform bacteria and Escherichia coli were more common in major area (MA) 1. Children (0-19 years) had a greater chance of living in poverty (OR 3.36; 95% CI: 2.50- 4.52;