Lipidomics for robust high performance process development

As the biopharmaceutical industry reduces the risk of potential contaminations by adventitious agents and increases process yields, high performance cell culture processes have been developed that rely on animal-free peptide-free, protein-free chemically defined and lipid-free media. These processes rely on cell lines that have been adapted to these lipid-free production conditions and have developed very effective lipid production capacities. These lipid-production capacities result in new challenges in the harvest and purification steps such as filterability, ability to clean resins and resin reuse. This oral presentation will show case how lipidomics can provide insights and opportunities to control the interactions between high performance bioreactor production processes, harvest conditions and purification. Results obtained across large scale production processes of three different monoclonal antibodies will be displayed. The importance of controlling lipid biosynthesis and the presence of lipids in the cell culture fluid prior to affinity capture chromatography will be discussed. Three different control strategies will be showcased and their pros and cons in terms of process yields, robustness of the harvest and impact on the purification process post-harvest explaine

An Improved uvby-Metallicity Calibration for Metal-Rich Stars

We present an improved uvby-metallicity relation calibrated for F, G, and early K dwarfs, and an analogous uvby-T(eff) relation, both derived using a Levenberg-Marquardt minimization scheme. Our calibrations are based on 1533 stars which appear in both the Cayrel de Strobel (2001) metallicity compilation, and in the Hauck-Mermilliod (1998) catalog of uvby photometry. We also examine the speculative possibility of using uvby photometry to produce a uvby-planeticity calibration. We conclude that while there is likely no strong photometric indicator of the presence or absence of short-period planets, the possibility of a spectroscopic indicator of planeticity is well worth examining.Comment: 9 pages, 4 figures, accepted in ApJ Letter

Complete Genome Sequence of the Piezophilic, Mesophilic, Sulfate-Reducing Bacterium Desulfovibrio hydrothermalis AM13(T.).

International audienceDesulfovibrio hydrothermalis AM13(T) is a piezophilic, mesophilic, hydrogenotrophic sulfate-reducing bacterium collected from a deep-sea hydrothermal chimney on the East Pacific Rise (2,600 m depth, 13°N). We report the genome sequence of this bacterium, which includes a 3,702,934-bp chromosome and a circular plasmid of 5,328 bp

Real and virtual biological science living laboratory for science teachers' formation : promoting global scientific literacy and critical thinking for sustainable development

Global attempts to renew scientific education aim to stop the decline of young people's interest in science and technology, and to promote the development of citizens' scientific literacy for sustainable development. Among other changes, these aims require the adaptation of K12 Biological Science Teacher’s training to meet the new objectives. Scientific literacy involves knowing science and how knowledge is developed and validated, recognizing the interactions between science, technology and society, that is, the nature of science (NoS; a set of meta-scientific contents that encompass historical, epistemological and sociological aspects of science with great value for scientific education). It also involves grasping of cognitive skills underlying critical thinking (CT; a set of cognitive abilities, including self-regulation and metacognitive processes) and creative problem solving. Therefore, scientific literacy contributes to making informed decisions, facilitating the participation of citizens in situations and dilemmas of scientific tenor. In addition, CT is closely related to the performance of educators in their professional work. Particularly, in the teaching of science, CT skills favour and enhance the learning of concepts and theories linked not only to science but also to the NoS. Considering the current conditions of middle-higher K12 Biological Science Teachers’ formation and classrooms´ limitations in our country and the region, we propose a pilot project aiming to promote the transformation of initial teachers´ training, seeking to improve the development of CT skills and to deepen NoS comprehension. It will involve the immersion of K12 Biological Science Teacher students in Biological Science Living Physical and "mirror" Virtual Reality Laboratories. These laboratories will be equipped with "do it yourself" (DIY), "do it with others" (DIWO) and "bring your own device" (BYOD) technologies for the implementation of research-type activities framed in the philosophy of the "fabrication laboratories". The virtual platform will also comprise a library with didactic resources under permissive licenses to ensure a broader impact. Within these environments, K12 Biological Science Teacher students will engage in the creation of didactic units involving problem solving and knowledge building in parallel to deeper understanding of scientific processes. We also hope to promote the creativity and innovation of the participants, and the appropriation of DIY/DIWO/BYOD and virtual reality technologies as educational resources in the classroom and everyday life. Thanks to the virtual environment, this approach would also allow to reach both National and International K12 Biological Science Teacher students and graduate Biological Science Teachers. Considering the universal access to the Internet and free access to educational platforms in several countries, we also hope to impact on the non-formal and informal Biological Science education and contribute to achieving quality education for all (Objective # 4 of the Agenda for Sustainable Development 2030, UNESCO) beyond geographical and cultural barriers. This pilot project will be implemented by an interinstitutional, multidisciplinary and international team. It will capitalize on confluent groups´ previous experience and complementary strengths in Science didactics (particularly biology), engineering, arts, virtual reality, fabrication, as well as open hardware and open software culture. The experimental approach corresponds to a quasi-experimental pre-test/post-test design with control groups, and formative and summative evaluation. As a result of the implementation of this educational innovation we expect to contribute to the improvement of Biological Science Teachers students´ CT skills and promote their active involvement in practical activities that should enhance their professional activity

Complete genome sequence of a New Zealand Mycobacterium tuberculosis strain responsible for ongoing transmission over the past 30 years.

We report here the complete genome sequence of Mycobacterium tuberculosis strain Colonial S-type 1 (CS1), which has been responsible for ongoing outbreaks of tuberculosis in New Zealand over the past 30 years. CS1 appears to be highly transmissible, with greater rates of progression to active disease, compared to other circulating M. tuberculosis strains; therefore, comparison of its genomic content is of interest

Developmental origin and maintenance of distinct testicular macrophage populations

International audienceTesticular macrophages (tM phi) are the principal immune cells of the mammalian testis. Beyond classical immune functions, they have been shown to be important for organogenesis, spermatogenesis, and male hormone production. In the adult testis, two different macrophage populations have been identified based on their distinct tissue localization and morphology, but their developmental origin and mode of homeostatic maintenance are unknown. In this study, we use genetic lineage-tracing models and adoptive transfer protocols to address this question. We show that embryonic progenitors give rise to the interstitial macrophage population, whereas peritubular macrophages are exclusively seeded postnatally in the prepuberty period from bone marrow (BM)-derived progenitors. As the proliferative capacity of interstitial macrophages declines, BM progenitors also contribute to this population. Once established, both the peritubular and interstitial macrophage populations exhibit a long life span and a low turnover in the steady state. Our observations identify distinct developmental pathways for two different tM phi populations that have important implications for the further dissection of their distinct roles in organ homeostasis and testicular function

Cohesin mutations are synthetic lethal with stimulation of WNT signaling

Mutations in genes encoding subunits of the cohesin complex are common in several cancers, but may also expose druggable vulnerabilities. We generated isogenic MCF10A cell lines with deletion mutations of genes encoding cohesin subunits SMC3, RAD21, and STAG2 and screened for synthetic lethality with 3009 FDA-approved compounds. The screen identified several compounds that interfere with transcription, DNA damage repair and the cell cycle. Unexpectedly, one of the top 'hits' was a GSK3 inhibitor, an agonist of Wnt signaling. We show that sensitivity to GSK3 inhibition is likely due to stabilization of β-catenin in cohesin-mutant cells, and that Wnt-responsive gene expression is highly sensitized in STAG2-mutant CMK leukemia cells. Moreover, Wnt activity is enhanced in zebrafish mutant for cohesin subunits stag2b and rad21. Our results suggest that cohesin mutations could progress oncogenesis by enhancing Wnt signaling, and that targeting the Wnt pathway may represent a novel therapeutic strategy for cohesin-mutant cancers.Health Research Council of New Zealand (15/229) Julia A Horsfield Health Research Council of New Zealand (19/415) Ross D Hannan Julia A Horsfield Associazione Italiana per la Ricerca sul Cancro (IG23284) Antonio Musio The Maurice Wilkins centre for Molecular Biodiscovery (3705733) Jisha Antony Julia A Horsfiel

A generic method for estimating and smoothing multispecies biodiversity indices using intermittent data

Biodiversity indicators summarise extensive, complex ecological data sets and are important in influencing government policy. Component data consist of time-varying indices for each of a number of different species. However, current biodiversity indicators suffer from multiple statistical shortcomings. We describe a state-space formulation for new multispecies biodiversity indicators, based on rates of change in the abundance or occupancy probability of the contributing individual species. The formulation is flexible and applicable to different taxa. It possesses several advantages, including the ability to accommodate the sporadic unavailability of data, incorporate variation in the estimation precision of the individual species’ indices when appropriate, and allow the direct incorporation of smoothing over time. Furthermore, model fitting is straightforward in Bayesian and classical implementations, the latter adopting either efficient Hidden Markov modelling or the Kalman filter. Conveniently, the same algorithms can be adopted for cases based on abundance or occupancy data—only the subsequent interpretation differs. The procedure removes the need for bootstrapping which can be prohibitive. We recommend which of two alternatives to use when taxa are fully or partially sampled. The performance of the new approach is demonstrated on simulated data, and through application to three diverse national UK data sets on butterflies, bats and dragonflies. We see that uncritical incorporation of index standard errors should be avoided

Multispacer Sequence Typing Relapsing Fever Borreliae in Africa

In Africa, relapsing fevers are caused by four cultured species: Borrelia crocidurae, Borrelia duttonii, Borrelia hispanica and Borrelia recurrentis. These borreliae are transmitted by the bite of Ornithodoros soft ticks except for B. recurrentis which is transmitted by louse Pediculus humanus. They cause potentially undifferentiated fever infection and co-infection with malaria could also occur. The exact prevalence of each Borrelia is unknown and overlaps between B. duttonii and B. crocidurae have been reported. The lack of tools for genotyping these borreliae limits knowledge concerning their epidemiology. We developed multispacer sequence typing (MST) and applied it to blood specimens infected by B. recurrentis (30 specimens), B. duttonii (18 specimens) and B. crocidurae (13 specimens), delineating these 60 strains and the 3 type strains into 13 species-specific spacer types. B. crocidurae strains were classified into 8 spacer types, B. duttonii into 3 spacer types and B. recurrentis into 2 spacer types. These findings provide the proof-of-concept that that MST is a reliable tool for identification and genotyping relapsing fever borreliae in Africa

Contributions to conservation outcomes by natural history museum-led citizen science: Examining evidence and next steps

publisher: Elsevier articletitle: Contributions to conservation outcomes by natural history museum-led citizen science: Examining evidence and next steps journaltitle: Biological Conservation articlelink: http://dx.doi.org/10.1016/j.biocon.2016.08.040 content_type: article copyright: © 2016 The Authors. Published by Elsevier Ltd.The file attached is the published version of the article