As-yet-uncultivated oral bacteria: breadth and association with oral and extra-oral diseases

It has been shown that 40–60% of the bacteria found in different healthy and diseased oral sites still remain to be grown in vitro, phenotypically characterized, and formally named as species. The possibility exists that these as-yet-uncultivated bacteria play important ecological roles in oral bacterial communities and may participate in the pathogenesis of several oral infectious diseases. There is also a potential for these as-yet-uncultivated oral bacteria to take part in extra-oral infections. For a comprehensive characterization of physiological and pathogenic properties as well as antimicrobial susceptibility of individual bacterial species, strains need to be grown in pure culture. Advances in culturing techniques have allowed the cultivation of several oral bacterial taxa only previously known by a 16S rRNA gene sequence signature, and novel species have been proposed. There is a growing need for developing improved methods to cultivate and characterize the as-yet-uncultivated portion of the oral microbiome so as to unravel its role in health and disease

Quality assurance, benchmarking, assessment and mutual international recognition of qualifications

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CORE: A Phylogenetically-Curated 16S rDNA Database of the Core Oral Microbiome

Comparing bacterial 16S rDNA sequences to GenBank and other large public databases via BLAST often provides results of little use for identification and taxonomic assignment of the organisms of interest. The human microbiome, and in particular the oral microbiome, includes many taxa, and accurate identification of sequence data is essential for studies of these communities. For this purpose, a phylogenetically curated 16S rDNA database of the core oral microbiome, CORE, was developed. The goal was to include a comprehensive and minimally redundant representation of the bacteria that regularly reside in the human oral cavity with computationally robust classification at the level of species and genus. Clades of cultivated and uncultivated taxa were formed based on sequence analyses using multiple criteria, including maximum-likelihood-based topology and bootstrap support, genetic distance, and previous naming. A number of classification inconsistencies for previously named species, especially at the level of genus, were resolved. The performance of the CORE database for identifying clinical sequences was compared to that of three publicly available databases, GenBank nr/nt, RDP and HOMD, using a set of sequencing reads that had not been used in creation of the database. CORE offered improved performance compared to other public databases for identification of human oral bacterial 16S sequences by a number of criteria. In addition, the CORE database and phylogenetic tree provide a framework for measures of community divergence, and the focused size of the database offers advantages of efficiency for BLAST searching of large datasets. The CORE database is available as a searchable interface and for download at http://microbiome.osu.edu

ExoClock Project: An open platform for monitoring the ephemerides of Ariel targets with contributions from the public

The Ariel mission will observe spectroscopically around 1000 exoplanets to further characterise their atmospheres. For the mission to be as efficient as possible, a good knowledge of the planets' ephemerides is needed before its launch in 2028. While ephemerides for some planets are being refined on a per-case basis, an organised effort to collectively verify or update them when necessary does not exist. In this study, we introduce the ExoClock project, an open, integrated and interactive platform with the purpose of producing a confirmed list of ephemerides for the planets that will be observed by Ariel. The project has been developed in a manner to make the best use of all available resources: observations reported in the literature, observations from space instruments and, mainly, observations from ground-based telescopes, including both professional and amateur observatories. To facilitate inexperienced observers and at the same time achieve homogeneity in the results, we created data collection and validation protocols, educational material and easy to use interfaces, open to everyone. ExoClock was launched in September 2019 and now counts over 140 participants from more than 15 countries around the world. In this release, we report the results of observations obtained until the 15h of April 2020 for 119 Ariel candidate targets. In total, 632 observations were used to either verify or update the ephemerides of 83 planets. Additionally, we developed the Exoplanet Characterisation Catalogue (ECC), a catalogue built in a consistent way to assist the ephemeris refinement process. So far, the collaborative open framework of the ExoClock project has proven to be highly efficient in coordinating scientific efforts involving diverse audiences. Therefore, we believe that it is a paradigm that can be applied in the future for other research purposes, too

Mentoring Impact on Leader Efficacy Development: A Field Experiment

While practitioners and scholars tout the importance of mentorship in leader development, few studies have empirically determined whether mentoring actually positively impacts a leader’s development, and if so, in what ways. In a longitudinal field experiment, we examined how a targeted mentorship program that unfolded over 6 months enhanced the development of protégés’ leader efficacy and performance. Results showed that the targeted mentorship intervention increased protégés’ level of leader efficacy more than a comparison intervention that was based on a more eclectic leadership education program delivered in a group setting. Leader efficacy then predicted rated leader performance. Both protégés’ preferences for feedback and trust in the mentor served as important moderators in contributing to the development of leader efficacy. Findings from this longitudinal field experiment could be used by educational institutions and other organizations to enhance their mentorship programs in content, focus, and evaluation of impact

ExoClock Project III: 450 new exoplanet ephemerides from ground and space observations

The ExoClock project has been created with the aim of increasing the efficiency of the Ariel mission. It will achieve this by continuously monitoring and updating the ephemerides of Ariel candidates over an extended period, in order to produce a consistent catalogue of reliable and precise ephemerides. This work presents a homogenous catalogue of updated ephemerides for 450 planets, generated by the integration of $\sim$18000 data points from multiple sources. These sources include observations from ground-based telescopes (ExoClock network and ETD), mid-time values from the literature and light-curves from space telescopes (Kepler/K2 and TESS). With all the above, we manage to collect observations for half of the post-discovery years (median), with data that have a median uncertainty less than one minute. In comparison with literature, the ephemerides generated by the project are more precise and less biased. More than 40\% of the initial literature ephemerides had to be updated to reach the goals of the project, as they were either of low precision or drifting. Moreover, the integrated approach of the project enables both the monitoring of the majority of the Ariel candidates (95\%), and also the identification of missing data. The dedicated ExoClock network effectively supports this task by contributing additional observations when a gap in the data is identified. These results highlight the need for continuous monitoring to increase the observing coverage of the candidate planets. Finally, the extended observing coverage of planets allows us to detect trends (TTVs - Transit Timing Variations) for a sample of 19 planets. All products, data, and codes used in this work are open and accessible to the wider scientific community.Comment: Recommended for publication to ApJS (reviewer's comments implemented). Main body: 13 pages, total: 77 pages, 7 figures, 7 tables. Data available at http://doi.org/10.17605/OSF.IO/P298

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery