Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants

A pair production telescope for medium-energy gamma-ray polarimetry

We describe the science motivation and development of a pair production telescope for medium-energy (∼5–200 MeV) gamma-ray polarimetry. Our instrument concept, the Advanced Energetic Pair Telescope (AdEPT), takes advantage of the Three-Dimensional Track Imager, a low-density gaseous time projection chamber, to achieve angular resolution within a factor of two of the pair production kinematics limit (∼0.6° at 70 MeV), continuum sensitivity comparable with the Fermi-LAT front detector (<3 × 10−6 MeV cm−2 s−1 at 70 MeV), and minimum detectable polarization less than 10% for a 10 mCrab source in 106 s.submittedVersionFil: Hunter, Stanley D. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Bloser, Peter F. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Depaola, Gerardo Osvaldo. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Dion, Michael P. Department of Energy. Office of Science. Pacific Northwest National Laboratory; Estados Unidos de América.Fil: DeNolfo, Georgia A. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Hanu, Andrei. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Iparraguirre, Lorenzo Marcos. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Legere, Jason. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Longo, Francesco. Università Degli Studi de Trieste. Dipartimento di fisica; Italia.Fil: McConnell, Mark L. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Nowicki, Suzanne F. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Nowicki, Suzanne F. University of Maryland, Baltimore County. Department of Physics; Estados Unidos de América.Fil: Ryan, James M. University of New Hampshire. Institute for the Study of Earth, Oceans, and Space. Space Science Center; Estados Unidos de América.Fil: Son, Seunghee. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Fil: Son, Seunghee. University of Maryland, Baltimore County. Department of Physics; Estados Unidos de América.Fil: Stecker, Floyd W. National Aeronautics and Space Administration. Goddard Space Flight Center; Estados Unidos de América.Física de Partículas y Campo

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

COVID-19 first lockdown as a window into language acquisition : associations between caregiver-child activities and vocabulary gains

The COVID-19 pandemic, and the resulting closure of daycare centers worldwide, led to unprecedented changes in children’s learning environments. This period of increased time at home with caregivers, with limited access to external sources (e.g., daycares) provides a unique opportunity to examine the associations between the caregiver-child activities and children’s language development. The vocabularies of 1742 children aged8-36 months across 13 countries and 12 languages were evaluated at the beginning and end of the first lockdown period in their respective countries(from March to September 2020). Children who had less passive screen exposure and whose caregivers read more to them showed larger gains in vocabulary development during lockdown, after controlling for SES and other caregiver-child activities. Children also gained more words than expected (based on normative data) during lockdown; either caregivers were more aware of their child’s development or vocabulary development benefited from intense caregiver-child interaction during lockdown

COVID-19 first lockdown as a window into language acquisition: Associations between caregiver-child activities and vocabulary gains

The COVID-19 pandemic, and the resulting closure of daycare centers worldwide, led to unprecedented changes in children’s learning environments. This period of increased time at home with caregivers, with limited access to external sources (e.g., daycares) provides a unique opportunity to examine the associations between the caregiver-child activities and children’s language development. The vocabularies of 1742 children aged 8-36 months across 13 countries and 12 languages were evaluated at the beginning and end of the first lockdown period in their respective countries (from March to September 2020). Children who had less passive screen exposure and whose caregivers read more to them showed larger gains in vocabulary development during lockdown, after controlling for SES and other caregiver-child activities. Children also gained more words than expected (based on normative data) during lockdown; either caregivers were more aware of their child’s development or vocabulary development benefited from intense caregiver-child interaction during lockdown

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood

Service-users’ perspectives of link worker social prescribing: a qualitative follow-up study

Background: Social prescribing enables health-care professionals to address non-medical causes of ill-health by harnessing the resources of the voluntary and community sectors in patient care. Although increasingly popular in the UK, evidence for the effectiveness of social prescribing is inconclusive and longer-term studies are needed. This study aimed to explore experiences of social prescribing among people with long-term conditions one to two years after their initial engagement with a social prescribing service. Methods: Qualitative methods comprising semi-structured follow-up interviews were conducted with 24 users of a link worker social prescribing service who had participated in an earlier study. Participants were aged between 40 and 74 years and were living in a socioeconomically-deprived area of North East England. Results: Participants reported reduced social isolation and improvements in their condition management and health-related behaviours. However, many participants had experienced setbacks, requiring continued support to overcome problems due to multi-morbidity, family circumstances and social, economic or cultural factors. Findings indicated that, in this sample of people facing complex health and socioeconomic issues, longer-term intervention and support was required. Features of the link worker social prescribing intervention that were positively appraised by participants, included a highly personalised service to reflect individual goal setting priorities and a focus on gradual and holistic change dealing with issues beyond health. The important role of a strong and supportive relationship with an easily-accessible link worker in promoting sustained behaviour change highlights the importance of link worker continuity. A lack of suitable and accessible voluntary and community services for onward referral acted as a barrier to involvement for some participants. Conclusions: This study highlights issues of interest to commissioners and providers of social prescribing. Engagement with social prescribing for up to two years was examined and continued involvement was identified for those with complex issues, suggesting that a long-term intervention is required. The availability of onward referral services is an important consideration for social prescribing in a time of constrained public spending. From a research perspective, the range of improvements and their episodic nature suggest that the evaluation of social prescribing interventions requires both quantitative and qualitative data collected longitudinally