Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in ~20% of HIV-1-infected individuals, and details of their generation could provide a roadmap for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from time of infection. The mature antibody, CH103, neutralized ~55% of HIV-1 isolates, and its co-crystal structure with gp120 revealed a novel loop-based mechanism of CD4-binding site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the CH103-lineage unmutated common ancestor avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data elucidate the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies and provide insights into strategies to elicit similar antibodies via vaccination

Hyperspectral Earth observation from IASI: Five years of accomplishments

The Infrared Atmospheric Sounding Interferometer (IASI) forms the main infrared sounding component of the European Organisation for the Exploitation of Meteorological Satellites's (EUMETSAT's) Meteorological Operation (MetOp)-A satellite (Klaes et al. 2007), which was launched in October 2006. This article presents the results of the first 4 yr of the operational IASI mission. The performance of the instrument is shown to be exceptional in terms of calibration and stability. The quality of the data has allowed the rapid use of the observations in operational numerical weather prediction (NWP) and the development of new products for atmospheric chemistry and climate studies, some of which were unexpected before launch. The assimilation of IASI observations in NWP models provides a significant forecast impact; in most cases the impact has been shown to be at least as large as for any previous instrument. In atmospheric chemistry, global distributions of gases, such as ozone and carbon monoxide, can be produced in near–real time, and short-lived species, such as ammonia or methanol, can be mapped, allowing the identification of new sources. The data have also shown the ability to track the location and chemistry of gaseous plumes and particles associated with volcanic eruptions and fires, providing valuable data for air quality monitoring and aircraft safety. IASI also contributes to the establishment of robust long-term data records of several essential climate variables. The suite of products being developed from IASI continues to expand as the data are investigated, and further impacts are expected from increased use of the data in NWP and climate studies in the coming years. The instrument has set a high standard for future operational hyperspectral infrared sounders and has demonstrated that such instruments have a vital role in the global observing system

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683–691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671–5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies