HTLV-1 clonality during chronic infection and BLV clonality during primary infection

peer reviewedaudience: researcherHTLV-1 clonality during chronic infection and BLV clonality during primary infection Nicolas A Gillet1,2*, Carol Hlela1, Tine Verdonck3, Eduardo Gotuzzo3, Daniel Clark3, Sabrina Rodriguez2, Nirav Malani4, Anat Melamed1, Niall Gormley5, Richard Carter5, David Bentley5, Charles Berry6, Frederic D Bushman4, Graham P Taylor7, Luc Willems2, Charles R M Bangham1 1Department of Immunology, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. 2Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg), Liège, 4000, Belgium. 3Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 4Department of Microbiology, University of Pennsylvania School of Medicine, Pennsylvania, Philadelphia, PA, 19104, USA. 5Illumina, Chesterford Research Park, Essex, Little Chesterford, CB10 1XL, UK. 6University of California, California, La Jolla San Diego, CA, 92093-0901, USA. 7Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the abundance of HTLV-1-infected clones remain unknown. We demonstrate that negative selection dominates during chronic infection, favouring establishment of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. We postulated that this selection occurred mainly during the primary infection. We are testing this hypothesis in an animal model by studying the BLV clonality during the primary infection in cows. By measuring the proviral load, the anti-BLV immune response and the BLV clonality we aim to quantify the impact of the immune response on the rate of infectious spread and on the selection of proviruses inserted in a particular genomic environment. Co-infection with Strongyloides stercoralis or Staphylococcus appears to be another risk factor for the development of HTLV-1 associated diseases. We observed that HTLV-1 clonality is altered by co-infection with these pathogens with an increase of both the number and the abundance of the infected T-cell clones. The genomic characteristics of the proviral integration sites in the most abundant clones differ significantly between co-infected individuals and those with HTLV-1 alone, implying the existence of different selection forces in co-infected patients. The rate of appearance of new clones in patients co-infected with Strongyloides stercoralis is higher than in patients with HTLV-1 alone. By comparing skin lesions and blood samples from patients with Infective Dermatitis associated with HTLV-1 (IDH), we observed a significant proportion of distinct infected clones between the two compartments. The skin lesions seem to be a site for HTLV-1 infectious spread

School Toileting Environment, Bullying, and Lower Urinary Tract Symptoms in a Population of Adolescent and Young Adult Girls:Preventing Lower Urinary Tract Symptoms Consortium Analysis of Avon Longitudinal Study of Parents and Children

AIM: Little is known about the association of the school toilet environment with voiding behaviors and lower urinary tract symptoms (LUTS) in adolescents. The purpose of the present longitudinal, secondary data analysis is to examine whether the school toilet environment at age 13, including bullying, is associated with LUTS at ages 13 and 19. METHODS: The sample comprised 3962 female participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). At age 13, participants reported on 7 school toilet environment characteristics and a range of LUTS items. At age 19, participants completed the Bristol Female Lower Urinary Tract Symptoms (ICIQ-BFLUTS) questionnaire. RESULTS: All toilet environmental factors were associated with at least one LUTS outcome at age 13. Holding behavior was associated with all school toilet environmental factors, with odds ratios (ORs) ranging from 1.36 (95% CI: 1.05, 1.76) for dirty toilets to 2.38 (95% CI: 1.60, 3.52) for feeling bullied at toilets. Bullying was associated with all LUTS symptoms; ORs ranged from 1.60 (95% CI: 1.04, 2.07) for nocturia to 2.90 (95% CI: 1.77, 4.75) for urgency. Associations between age 13 school toilets and age 19 LUTS were in the same direction as age 13 LUTS. CONCLUSION: This is the first examination of associations between school toilets and LUTS. Toileting environments were cross-sectionally associated with LUTS in adolescent girls. While further work is needed to determine whether these associations are causal, school toilet environments are modifiable and thus a promising target for LUTS prevention

Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation.

The Consensus Coding Sequence (CCDS) project provides a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assembly in genome annotations produced independently by NCBI and the Ensembl group at EMBL-EBI. This dataset is the product of an international collaboration that includes NCBI, Ensembl, HUGO Gene Nomenclature Committee, Mouse Genome Informatics and University of California, Santa Cruz. Identically annotated coding regions, which are generated using an automated pipeline and pass multiple quality assurance checks, are assigned a stable and tracked identifier (CCDS ID). Additionally, coordinated manual review by expert curators from the CCDS collaboration helps in maintaining the integrity and high quality of the dataset. The CCDS data are available through an interactive web page (https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi) and an FTP site (ftp://ftp.ncbi.nlm.nih.gov/pub/CCDS/). In this paper, we outline the ongoing work, growth and stability of the CCDS dataset and provide updates on new collaboration members and new features added to the CCDS user interface. We also present expert curation scenarios, with specific examples highlighting the importance of an accurate reference genome assembly and the crucial role played by input from the research community. Nucleic Acids Res 2018 Jan 4; 46(D1):D221-D228

Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization

BACKGROUND: In order to establish a consistent method for brachial artery reactivity assessment, we analyzed commonly used approaches to the test and their effects on the magnitude and time-course of flow mediated dilation (FMD), and on test variability and repeatability. As a popular and noninvasive assessment of endothelial function, several different approaches have been employed to measure brachial artery reactivity with B-mode ultrasound. Despite some efforts, there remains a lack of defined normal values and large variability in measurement technique. METHODS: Twenty-six healthy volunteers underwent repeated brachial artery diameter measurements by B-mode ultrasound. Following baseline diameter recordings we assessed endothelium-dependent flow mediated dilation by inflating a blood pressure cuff either on the upper arm (proximal) or on the forearm (distal). RESULTS: Thirty-seven measures were performed using proximal occlusion and 25 with distal occlusion. Following proximal occlusion relative to distal occlusion, FMD was larger (16.2 ± 1.2% vs. 7.3 ± 0.9%, p < 0.0001) and elongated (107.2 s vs. 67.8 s, p = 0.0001). Measurement of the test repeatability showed that differences between the repeated measures were greater on average when the measurements were done using the proximal method as compared to the distal method (2.4%; 95% CI 0.5–4.3; p = 0.013). CONCLUSION: These findings suggest that forearm compression holds statistical advantages over upper arm compression. Added to documented physiological and practical reasons, we propose that future studies should use forearm compression in the assessment of endothelial function

Automobile Prices, Gasoline Prices, and Consumer Demand for Fuel Economy

The relationship between gasoline prices and the demand for vehicle fuel efficiency is important for environmental policy but poorly understood in the academic literature. We provide empirical evidence that automobile manufacturers price as if consumers respond to gasoline prices. We derive a reduced-form regression equation from theoretical micro-foundations and estimate the equation with nearly 300,000 vehicle-week-region observations over the period 2003-2006. We find that vehicle prices generally decline in the gasoline price. The decline is larger for inefficient vehicles, and the prices of particularly efficient vehicles actually rise. Structural estimation that ignores these effects underestimates consumer preferences for fuel efficiency

High-Risk Histopathological Features of Retinoblastoma following Primary Enucleation: A Global Study of 1426 Patients from 5 Continents

Purpose: To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents // Methods: Retrospective study of 1426 primarily enucleated RB eyes from five continents // Results: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients. // Conclusion: There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity