Sixty years of genome biology

Sixty years after Watson and Crick published the double helix model of DNA's structure, thirteen members of Genome Biology's Editorial Board select key advances in the field of genome biology subsequent to that discovery

Genome Sequence of the Mesophilic Thermotogales Bacterium Mesotoga prima MesG1.Ag.4.2 Reveals the Largest Thermotogales Genome To Date

Here we describe the genome of Mesotoga prima MesG1.Ag4.2, the first genome of a mesophilic Thermotogales bacterium. Mesotoga prima was isolated from a polychlorinated biphenyl (PCB)-dechlorinating enrichment culture from Baltimore Harbor sediments. Its 2.97 Mb genome is considerably larger than any previously sequenced Thermotogales genomes, which range between 1.86 and 2.30 Mb. This larger size is due to both higher numbers of protein-coding genes and larger intergenic regions. In particular, the M. prima genome contains more genes for proteins involved in regulatory functions, for instance those involved in regulation of transcription. Together with its closest relative, Kosmotoga olearia, it also encodes different types of proteins involved in environmental and cell–cell interactions as compared with other Thermotogales bacteria. Amino acid composition analysis of M. prima proteins implies that this lineage has inhabited low-temperature environments for a long time. A large fraction of the M. prima genome has been acquired by lateral gene transfer (LGT): a DarkHorse analysis suggests that 766 (32%) of predicted protein-coding genes have been involved in LGT after Mesotogadiverged from the other Thermotogales lineages. A notable example of a lineage-specific LGT event is a reductive dehalogenase gene—a key enzyme in dehalorespiration, indicating M. prima may have a more active role in PCB dechlorination than was previously assumed

Prevention and early detection of prostate cancer

This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression

Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

A 1.9 Earth Radius Rocky Planet and the Discovery of a Non-Transiting Planet in the Kepler-20 System*

Kepler-20 is a solar-type star (V = 12.5) hosting a compact system of five transiting planets, all packed within the orbital distance of Mercury in our own Solar System. A transition from rocky to gaseous planets with a planetary transition radius of ∼ 1.6 R⊕ has recently been proposed by several publications in the literature (Rogers 2015; Weiss& Marcy 2014). Kepler-20b (Rp ∼ 1.9 R⊕) has a size beyond this transition radius, however previous mass measurements were not sufficiently precise to allow definite conclusions to be drawn regarding its composition. We present new mass measurements of Kepler-20 three of the planets in the Kepler-20 system facilitated by 104 radial velocity measurements from the HARPS-N spectrograph and 30 archival Keck/HIRES observations, as well as an updated photometric analysis of the Kepler data and an asteroseismic analysis of the host star (M* = 0.948 ± 0.051 M☉ and R* = 0.964 ± 0.018 R☉).Kepler-20b is a 1.868+0.066 −0.034 R⊕ planet in a 3.7 day period with amass of 9.70+1.41 −1.44 M⊕ resulting in a mean density of 8.2 +1.5 −1.3 g cm−3 indicating a rocky composition with an iron to silicate ratio consistent with that of the Earth. This makes Kepler-20b the most massive planet with a rocky composition found to date. Furthermore, we report the discovery of an additional non-transiting planet with a minimum mass of 19.96+3.08 −3.61 M⊕ and an orbital period of ∼ 34 days in the gap between Kepler-20f (P ∼ 11 days) and Kepler-20d (P ∼78 days).PostprintPeer reviewe

Experiencing uncertainty – on the potential of groups and a group analytic approach for making management education more critical.

This document is the Accepted Manuscript. The final, definitive version of this paper has been published in Management Learning, November 2017, DOI: https://doi.org/10.1177/1350507617697868. Published by SAGE Publishing. All rights reserved.This article points to the potential of methods derived from group analytic practice for making management education more critical. It draws on the experience of running a professional doctorate for more experienced managers in a university in the UK over a 16 year period. Group analysis is informed by the highly social theories of S.H. Foulkes and draws heavily on psychoanalytic theory as well as sociology. First and foremost, though, it places our interdependence at the heart of the process of inquiry, and suggests that the most potent place for learning about groups, where we spend most of our lives, is in a group. The article prioritises three areas of management practice for which group analytic methods, as adapted for research environment, are most helpful: coping with uncertainty and the feelings of anxiety which this often arouses; thinking about leadership as a relational and negotiated activity, and encouraging reflexivity in managers. The article also points to some of the differences between the idea of the learning community and psychodynamic perspectives more generally and the limitations of group analytic methods in particular, which may pathologise resistance in the workplace.Peer reviewe

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents