Cross-protection of the Bivalent Human Papillomavirus (HPV) Vaccine Against Variants of Genetically Related High-Risk HPV Infections

BackgroundResults from the Costa Rica Vaccine Trial (CVT) demonstrated partial cross-protection by the bivalent human papillomavirus (HPV) vaccine, which targets HPV-16 and HPV-18, against HPV-31, -33, and -45 infection and an increased incidence of HPV-51 infection.MethodsA study nested within the CVT intention-to-treat cohort was designed to assess high-risk HPV variant lineage-specific vaccine efficacy (VE). The 2 main end points were (1) long-term incident infections persisting for ≥2 years and/or progression to high-grade squamous intraepithelial lesions (ie, cervical intraepithelial neoplasia grade 2/3 [CIN 2/3]) and (2) incident transient infections lasting for <2 years. For efficiency, incident infections due to HPV-16, -18, -31, -33, -35, -45, and -51 resulting in persistent infection and/or CIN 2/3 were matched (ratio, 1:2) to the more-frequent transient viral infections, by HPV type. Variant lineages were determined by sequencing the upstream regulatory region and/or E6 region.ResultsVEs against persistent or transient infections with HPV-16, -18, -33, -35, -45, and -51 did not differ significantly by variant lineage. As the possible exception, VEs against persistent infection and/or CIN 2/3 due to HPV-31 A/B and HPV-31C variants were -7.1% (95% confidence interval [CI], -33.9% to 0%) and 86.4% (95% CI, 65.1%-97.1%), respectively (P = .02 for test of equal VE). No difference in VE was observed by variant among transient HPV-31 infections (P = .68).ConclusionsOverall, sequence variation at the variant level does not appear to explain partial cross-protection by the bivalent HPV vaccine

The Mice at play in the CALIFA survey: A case study of a gas-rich major merger between first passage and coalescence

We present optical integral field spectroscopy (IFS) observations of the Mice, a major merger between two massive (>10^11Msol) gas-rich spirals NGC4676A and B, observed between first passage and final coalescence. The spectra provide stellar and gas kinematics, ionised gas properties and stellar population diagnostics, over the full optical extent of both galaxies. The Mice provide a perfect case study highlighting the importance of IFS data for improving our understanding of local galaxies. The impact of first passage on the kinematics of the stars and gas has been significant, with strong bars likely induced in both galaxies. The barred spiral NGC4676B exhibits a strong twist in both its stellar and ionised gas disk. On the other hand, the impact of the merger on the stellar populations has been minimal thus far: star formation induced by the recent close passage has not contributed significantly to the global star formation rate or stellar mass of the galaxies. Both galaxies show bicones of high ionisation gas extending along their minor axes. In NGC4676A the high gas velocity dispersion and Seyfert-like line ratios at large scaleheight indicate a powerful outflow. Fast shocks extend to ~6.6kpc above the disk plane. The measured ram pressure and mass outflow rate (~8-20Msol/yr) are similar to superwinds from local ULIRGs, although NGC4676A has only a moderate infrared luminosity of 3x10^10Lsol. Energy beyond that provided by the mechanical energy of the starburst appears to be required to drive the outflow. We compare the observations to mock kinematic and stellar population maps from a merger simulation. The models show little enhancement in star formation during and following first passage, in agreement with the observations. We highlight areas where IFS data could help further constrain the models.Comment: 23 pages, 13 figures, accepted to A&A. A version with a complete set of high resolution figures is available here: http://www-star.st-and.ac.uk/~vw8/resources/mice_v8_astroph.pd

Genetic Characterization of Human T-Cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of Adult T-Cell Leukemia/Lymphoma (ATL), the Tropical Spastic Paraparesis/HTLV-1-associated Myelopathy (TSP/HAM) and other inflammatory diseases, including dermatitis, uveitis, and myositis. It is estimated that 2–8% of the infected persons will develop a HTLV-1-associated disease during their lifetimes, frequently TSP/HAM. Thus far, there is not a specific treatment to this progressive and chronic disease. HTLV-1 has means of three transmission: (i) from mother to child during prolonged breastfeeding, (ii) between sexual partners and (iii) through blood transfusion. HTLV-1 has been characterized in 7 subtypes and the geographical distribution and the clinical impact of this infection is not well known, mainly in African population. HTLV-1 is endemic in sub-Saharan Africa. Mozambique is a country of southeastern Africa where TSP/HAM cases were reported. Recently, our group estimated the HTLV prevalence among Mozambican blood donors as 0.9%. In this work we performed a genetic analysis of HTLV-1 in blood donors and HIV/HTLV co-infected patients from Maputo, Mozambique. Our results showed the presence of three HTLV-1 clusters within the Cosmopolitan/Transcontinental subtype/subgroup. The differential rates of HIV-1/HTLV-1 co-infection in the three HTLV-1 clusters demonstrated the dynamic of the two viruses and the need for implementation of control measures focusing on both retroviruses

Low-Resolution Molecular Models Reveal the Oligomeric State of the PPAR and the Conformational Organization of Its Domains in Solution

The peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid and carbohydrate metabolism, and are targets of drugs approved for human use. Whereas the crystallographic structure of the complex of full length PPARγ and RXRα is known, structural alterations induced by heterodimer formation and DNA contacts are not well understood. Herein, we report a small-angle X-ray scattering analysis of the oligomeric state of hPPARγ alone and in the presence of retinoid X receptor (RXR). The results reveal that, in contrast with other studied nuclear receptors, which predominantly form dimers in solution, hPPARγ remains in the monomeric form by itself but forms heterodimers with hRXRα. The low-resolution models of hPPARγ/RXRα complexes predict significant changes in opening angle between heterodimerization partners (LBD) and extended and asymmetric shape of the dimer (LBD-DBD) as compared with X-ray structure of the full-length receptor bound to DNA. These differences between our SAXS models and the high-resolution crystallographic structure might suggest that there are different conformations of functional heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange experiments reveal that the heterodimer binding to DNA promotes more compact and less solvent-accessible conformation of the receptor complex

Active Electric Imaging: Body-Object Interplay and Object's “Electric Texture”

This article deals with the role of fish's body and object's geometry on determining the image spatial shape in pulse Gymnotiforms. This problem was explored by measuring local electric fields along a line on the skin in the presence and absence of objects. We depicted object's electric images at different regions of the electrosensory mosaic, paying particular attention to the perioral region where a fovea has been described. When sensory surface curvature increases relative to the object's curvature, the image details depending on object's shape are blurred and finally disappear. The remaining effect of the object on the stimulus profile depends on the strength of its global polarization. This depends on the length of the object's axis aligned with the field, in turn depending on fish body geometry. Thus, fish's body and self-generated electric field geometries are embodied in this “global effect” of the object. The presence of edges or local changes in impedance at the nearest surface of closely located objects adds peaks to the image profiles (“local effect” or “object's electric texture”). It is concluded that two cues for object recognition may be used by active electroreceptive animals: global effects (informing on object's dimension along the field lines, conductance, and position) and local effects (informing on object's surface). Since the field has fish's centered coordinates, and electrosensory fovea is used for exploration of surfaces, fish fine movements are essential to perform electric perception. We conclude that fish may explore adjacent objects combining active movements and electrogenesis to represent them using electrosensory information

COLOMBOS: Access Port for Cross-Platform Bacterial Expression Compendia

Background: Microarrays are the main technology for large-scale transcriptional gene expression profiling, but the large bodies of data available in public databases are not useful due to the large heterogeneity. There are several initiatives that attempt to bundle these data into expression compendia, but such resources for bacterial organisms are scarce and limited to integration of experiments from the same platform or to indirect integration of per experiment analysis results. Methodology/Principal Findings: We have constructed comprehensive organism-specific cross-platform expression compendia for three bacterial model organisms (Escherichia coli, Bacillus subtilis, and Salmonella enterica serovar Typhimurium) together with an access portal, dubbed COLOMBOS, that not only provides easy access to the compendia, but also includes a suite of tools for exploring, analyzing, and visualizing the data within these compendia. It is freely available at http://bioi.biw.kuleuven.be/colombos. The compendia are unique in directly combining expression information from different microarray platforms and experiments, and we illustrate the potential benefits of this direct integration with a case study: extending the known regulon of the Fur transcription factor of E. coli. The compendia also incorporate extensive annotations for both genes and experimental conditions; these heterogeneous data are functionally integrated in the COLOMBOS analysis tools to interactively browse and query the compendia not only for specific genes or experiments, but also metabolic pathways, transcriptional regulation mechanisms, experimental conditions, biological processes, etc. Conclusions/Significance: We have created cross-platform expression compendia for several bacterial organisms and developed a complementary access port COLOMBOS, that also serves as a convenient expression analysis tool to extract useful biological information. This work is relevant to a large community of microbiologists by facilitating the use of publicly available microarray experiments to support their research

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Targeted Inactivation of Cerberus Like-2 Leads to Left Ventricular Cardiac Hyperplasia and Systolic Dysfunction in the Mouse

Previous analysis of the Cerberus like 2 knockout (Cerl2(-/-)) mouse revealed a significant mortality during the first day after birth, mostly due to cardiac defects apparently associated with randomization of the left-right axis. We have however, identified Cerl2-associated cardiac defects, particularly a large increase in the left ventricular myocardial wall in neonates that cannot be explained by laterality abnormalities. Therefore, in order to access the endogenous role of Cerl2 in cardiogenesis, we analyzed the embryonic and neonatal hearts of Cerl2 null mutants that did not display a laterality phenotype. Neonatal mutants obtained from the compound mouse line Cer2(-/-)Fundacao para a Ciencia e Tecnologia (FCT); IBB/CBME [PEst-OE/EQB/LA0023/2011]; FCT [SFRH/BD/62081/2009]info:eu-repo/semantics/publishedVersio