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What are world class scientific outputs?

My talk to the PhD students NRP at the Doctoral Training Programme Summer Conference 2015, The Assembly House, Norwich, Thursday 18th June.

Notes and acknowledgments at http://kamounlab.tumblr.com/post/121748816600/what-are-world-class-science-outputs

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What are world class scientific outputs?

  1. 1. What are world class scientific outputs? Sophien Kamoun http:KamounLab.net @KamounLab
  2. 2. Why am I a scientist?
  3. 3. My inspiration… “Je cherche à comprendre” “I seek to understand” Jacques Monod
  4. 4. I appreciate the power of science… • There is a reality out there and science can unravel it • “We have a moral duty to distinguish sense from nonsense” – Massimo Pigliucci • Science is predictive – key difference between science and pseudoscience
  5. 5. …and my motivation is curiosity • As a scientist, I am in the business of knowledge • I have an addiction to knowledge. I need to know: How do living organisms work? How did they get this way? • My job is to generate knowledge to advance science and influence others to pursue new directions and generate their own knowledge • My job is also to communicate this knowledge
  6. 6. Communication We must communicate our discoveries to other scientists, the government, the public etc. ! Otherwise the impact will be quasi-nil
  7. 7. Publications! • Main medium through which we communicate our science • Writing forces you to think harder and precisely formulate your work and contributions • An archived document that enables others to be inspired and build on your research (or dispute it) • Publications come in many forms these days • Publish or perish!
  8. 8. How do we recognise world class publications?
  9. 9. confirmation influence / impact
  10. 10. How to evaluate papers? Judge publications on their own merit Don’t use journals as proxy Article-level metrics
  11. 11. The Leiden Manifesto for research metrics “Do not use journal-based metrics, such as Journal Impact Factors, as a surrogate measure of the quality of individual research articles, to assess an individual scientist’s contributions, or in hiring, promotion, or funding decisions.”
  12. 12. Death to the impact factor Misused and abused Crude statistically flawed metric Skewed by few highly cited papers
  13. 13. The weakening relationship between the Impact Factor and papers’ citations in the digital age George A. Lozano, Vincent Lariviere, Yves Gingras y = 0.0011x - 1.9418 r2 = 0.4666 y = 0.003x - 5.7759 r2 = 0.579 y = -0.0049x + 9.9863 r2 = 0.4788 0,00 0,05 0,10 0,15 0,20 0,25 0,30 0,35 1900 1920 1940 1960 1980 2000 2020 Annualcoefficientofdetermination(r2) Coefficient of determination (r2 ) between the impact factor of journals and the two-year citation rate of their papers from 1902 to 2009, for al and medical sciences journals. 0,25
  14. 14. Citations • Most popular article-level metric • Vary widely between fields of science • Review articles get more cited • Time dependent - take time to accrue • Retracted papers still get cited (zombie papers) • etc. • But impact somewhat correlates with citations - imagine a paper that’s hardly cited
  15. 15. Highly Cited Papers • Thomson Reuters Essential Science Indicators℠ (ESI) • Rank in top 1% by citations for field and year indexed in the Web of Science • 21 broad fields defined by sets of journals • Papers are weighed against others in the same cohort • One example of article level metrics
  16. 16. Where to publish? • Aim as high as you reasonably can but don't become obsessed with glamour magazines (glam-mags) • Is your work relevant to a broad readership or is it more appropriate to specialists? • Consider “fit” not just journal prestige • Do you like what you read in the journal? • Open access papers get more widely read and cited
  17. 17. • Journals have declining influence in the digital age • Open web: anybody can read your work if it’s open access • Rise of the megajournals and preprint archives
  18. 18. You want impact! • Impact is not just about publishing in glam-mags • reach out to a wider audience, media exposure etc. • Social media: twitter, facebook etc. • Alternative metrics
  19. 19. • Many bad papers get published in Nature, Science & Cell • Don’t assume it’s flawless because it’s in a glam-mag • Judge papers on their own merit • Remember, time will tell! A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus Felisa Wolfe-Simon,1,2 * Jodi Switzer Blum,2 Thomas R. Kulp,2 Gwyneth W. Gordon,3 Shelley E. Hoeft,2 Jennifer Pett-Ridge,4 John F. Stolz,5 Samuel M. Webb,6 Peter K. Weber,4 Paul C. W. Davies,1,7 Ariel D. Anbar,1,3,8 Ronald S. Oremland2 Life is mostly composed of the elements carbon, hydrogen, nitrogen, oxygen, sulfur, and phosphorus. Although these six elements make up nucleic acids, proteins, and lipids and thus the bulk of living matter, it is theoretically possible that some other elements in the periodic table could serve the same functions. Here, we describe a bacterium, strain GFAJ-1 of the Halomonadaceae, isolated from Mono Lake, California, that is able to substitute arsenic for phosphorus to sustain its growth. Our data show evidence for arsenate in macromolecules that normally contain phosphate, most notably nucleic acids and proteins. Exchange of one of the major bio-elements may have profound evolutionary and geochemical importance. B iological dependence on the six major nutrient elements carbon, hydrogen, nitro- gen, oxygen, sulfur, and phosphorus (P) is complemented by a selected array of other ele- ments, usually metals or metalloids present in trace quantities that serve critical cellular func- tions, such as enzyme co-factors (1). There are many cases of these trace elements substituting for one another. A few examples include the sub- stitution of tungsten for molybdenum and cad- mium for zinc in some enzyme families (2, 3) and copper for iron as an oxygen-carrier in some ar- thropods and mollusks (4). In these examples and others, the trace elements that interchange share chemical similarities that facilitate the swap. How- ever, there are no prior reports of substitutions for any of the six major elements essential for life. Here, we present evidence that arsenic can be incorporated into some early steps in the path- ways [(6) and references therein]. However, it is thought that downstream metabolic processes are generally not compatible with As-incorporating molecules because of differences in the reactiv- ities of P and As compounds (8). These down- stream biochemical pathways may require the more chemically stable P-based metabolites; the lifetimes of more easily hydrolyzed As-bearing analogs are thought to be too short. However, given the similarities of As and P—and by anal- ogy with trace element substitutions—we hypoth- esized that AsO4 3– could specifically substitute for PO4 3– in an organism possessing mechanisms to cope with the inherent instability of AsO4 3– compounds (6). Here, we experimentally tested this hypothesis by using AsO4 3– , combined with no added PO4 3– , to select for and isolate a mi- crobe capable of accomplishing this substitution. Geomicrobiology of GFAJ-1. Mono Lake, located in eastern California, is a hypersaline and alkaline water body with high dissolved arsenic concentrations [200 mM on average (9)]. We used lake sediments as inocula into an aerobic defined artificial medium at pH 9.8 (10, 11) containing 10 mM glucose, vitamins, and trace metals but no added PO4 3– or any additional complex organic supplements (such as yeast extract or peptone), with a regimen of increasing AsO4 3– additions initially spanning the range from 100 mM to 5 mM. These enrichments were taken through many decimal-dilution transfers, greatly reducing any potential carryover of autochthonous phosphorus 5µm CA 0.05 0.10 0.15 0.20 0.25 0.30 OD680 RESEARCH ARTICLE onJune16,2015www.sciencemag.orgadedfromonJune16,2015www.sciencemag.orgadedfromonJune16,2015www.sciencemag.orgadedfromonJune16,2015www.sciencemag.orgadedfrom ARTICLE doi:10.1038/nature12968 Stimulus-triggered fate conversion of somatic cells into pluripotency Haruko Obokata1,2,3 , Teruhiko Wakayama3 {, Yoshiki Sasai4 , Koji Kojima1 , Martin P. Vacanti1,5 , Hitoshi Niwa6 , Masayuki Yamato7 & Charles A. Vacanti1 Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency (STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of plu- ripotent cells. Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrange- ment analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection. STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes. Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, our findingsindicatethatepigeneticfatedeterminationofmammaliancellscanbemarkedlyconvertedinacontext-dependent manner by strong environmental cues. In the canalization view of Waddington’s epigenetic landscape, fates of somatic cells are progressively determined as cellular differentiation proceeds, like going downhill. It is generally believed that reversal of differentiated statusrequires artificial physical or genetic manipulation of nuclear function such as nuclear transfer1,2 or the introduction of multiple transcription factors3 . Here we investigated the question of whether somatic cells can undergo nuclear reprogramming simply in response to external triggers without direct nuclear manipulation. This type of situation is known to occur in plants—drastic environmental changescanconvertmaturesomaticcells(forexample,dissociatedcarrot cells) into immature blastema cells, from which a whole plant structure, including stalks and roots, develops in the presence of auxins4 . A chal- lengingquestioniswhetheranimalsomaticcellshaveasimilarpotential that emerges under special conditions. Over the past decade, the pres- ence of pluripotent cells (or closely relevant cell types) in adult tissues has been a matter of debate, for which conflicting conclusions have beenreportedbyvariousgroups5–11 .However,nostudysofarhasproven that such pluripotent cells can arise from differentiated somatic cells. HaematopoieticcellspositiveforCD45(leukocytecommonantigen)are typicallineage-committedsomaticcellsthatneverexpresspluripotency- related markers such as Oct4 unless they are reprogrammed12,13 . We therefore addressed the questionof whether splenic CD451 cells could acquire pluripotency by drastic changes in their external environment such as those caused by simple chemical perturbations. Low pH triggers fate conversion in somatic cells CD451 cells were sorted by fluorescence-activated cell sorting (FACS) from the lymphocyte fraction of postnatal spleens (1-week old) of C57BL/6 mice carrying an Oct4-gfp transgene14 , and were exposed to various types of strong, transient, physical and chemical stimuli (described below). We examined these cells for activation of the Oct4 promoter after culture for several days in suspension using DMEM/F12 medium supplemented with leukaemia inhibitory factor (LIF) and B27 (hereafter called LIF1B27 medium). Among the various perturbations, wewereparticularlyinterestedinlow-pHperturbationsfortworeasons. First, as shown below, low-pH treatment turned out to be most effective for the induction of Oct4. Second, classical experimental embryology hasshownthatatransientlow-pHtreatmentunder‘sublethal’conditions can alter the differentiation status of tissues. Spontaneous neural conver- sion from salamander animal caps by soaking the tissues in citrate-based acidic medium below pH 6.0 has been demonstrated previously15–17 . Without exposure to the stimuli, none of the cells sorted with CD45 expressedOct4-GFPregardlessofthecultureperiodinLIF1B27medium. In contrast, a 30-min treatment with low-pH medium (25-min incuba- tion followed by 5-min centrifugation; Fig. 1a; the most effective range was pH 5.4–5.8; Extended Data Fig. 1a) caused the emergence of sub- stantialnumbersofsphericalclustersthatexpressedOct4-GFPinday-7 culture(Fig.1b).SubstantialnumbersofGFP1 cellsappearedinallcases performed with neonatalsplenic cells (n 5 30 experiments). The emer- genceofOct4-GFP1 cellsattheexpenseofCD451 cellswasalsoobserved by flow cytometry (Fig. 1c, top, and Extended Data Fig. 1b, c). We next fractionated CD451 cells into populations positive and negative for CD90(Tcells),CD19(Bcells)andCD34(haematopoieticprogenitors18 ), and subjected them to low-pH treatment. Cells of these fractions, including T and B cells, generated Oct4-GFP1 cells at an efficacy com- parable to unfractionated CD451 cells (25–50% of surviving cells on day 7), except for CD341 haematopoietic progenitors19 , which rarely produced Oct4-GFP1 cells (,2%; Extended Data Fig. 1d). Among maintenance media for pluripotent cells20 , the appearance of Oct4-GFP1 cells was most efficient in LIF1B27 medium, and did not occur in mouse epiblast-derived stem-cell (EpiSC) medium21,22 (Extended Data Fig. 1e). The presence or absence of LIF during days 0–2 did not substantially affect the frequency of Oct4-GFP1 cell gen- eration on day 7 (Extended Data Fig. 1f), whereas the addition of LIF during days 4–7 was not sufficient, indicating that LIF dependency started during days 2–4. 1 Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 2 Laboratory for Cellular Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 3 Laboratory for Genomic Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 4 Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 5 Department of Pathology, Irwin Army Community Hospital, Fort Riley, Kansas 66442, USA. 6 Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 7 Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo 162-8666, Japan. {Present address: Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan. RETRACTED
  20. 20. #arseniclife - what happened? ! • Postpublication peer review (PPPR) • Addressed flaws of pre-pub peer review • Social media and blogs
  21. 21. #arseniclife - what happened? ! • Postpublication peer review (PPPR) • Addressed flaws of pre-pub peer review • Social media and blogs
  22. 22. M I C R O B I A L E C O L O G Y The microbiome of uncontacted Amerindians Jose C. Clemente,1,2 * Erica C. Pehrsson,3 * Martin J. Blaser,4,5 Kuldip Sandhu,5† Zhan Gao,5 Bin Wang,3 Magda Magris,6 Glida Hidalgo,6 Monica Contreras,7 Óscar Noya-Alarcón,6 Orlana Lander,8 Jeremy McDonald,9 Mike Cox,9 Jens Walter,10‡ Phaik Lyn Oh,10 Jean F. Ruiz,11 Selena Rodriguez,11 Nan Shen,1 Se Jin Song,12 Jessica Metcalf,12 Rob Knight,12,13§ Gautam Dantas,3,14 M. Gloria Dominguez-Bello5,7,11¶ Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a micro- biome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that western- ization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mo- bilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized popula- tions before globalization of modern practices affects potentially beneficial bacteria harbored in the human body. INTRODUCTION Host-microbial interactions are important determinants of host phys- iology, including immune responses, metabolic homeostasis, and be- havior (1–4). Microbiota transplantation can transfer phenotypes such as nutritional status from donor to recipient (5, 6), indicating that al- tered microbial communities can therefore cause, as well as result from, altered physiological states. Despite increasing evidence that the micro- biome has important roles in human health, we do not yet know the extent to which the human microbiome has changed during the adop- tion of life-styles associated with westernization. Here, we described the microbiome from Yanomami subjects in the Amazon with no previous report of contact with non-Yanomami. The Yanomami were originally mountain people who were first contacted in the mid-1960s, and who continue to live seminomadic hunter-gatherer life-styles in the Amazon jungle. In Venezuela, they inhabit a region protected from development, and many still inhabit uncharted villages in the vast mountainous Yanomami territory (7). These remote populations of hunter-gatherers have life-styles similar to those of our human ancestors, and are unex- posed to modern practices known to exert antimicrobial effects. For instance, pharmacologic-dose antibiotic exposure is nearly ubiq- uitous worldwide, and all human microbiota studied to date, remote or industrialized, harbor diverse antibiotic resistance (AR) genes (8, 9). Al- though AR genes have been computationally predicted in ancient oral microbiota (10), functional resistance from the preantibiotic era re- mains largely uncharacterized. These subjects from an uncontacted community therefore represent a unique proxy for the preantibiotic era human resistome. Here, we characterized the microbiome and resis- tome of these subjects, and compared them to those of othernon-isolated populations. Samples of the oral cavity (n = 28), forearm skin (n = 28), and feces (n = 12) were obtained from 34 of the 54 villagers (table S1) at thetimeofthefirstmedicalexpeditiontoanisolated,previouslyuncharted village in the High Orinoco state of Venezuela. The age of the subjects was between 4 and 50 years, as estimated by Yanomami health workers. 1 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 2 Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 3 Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. 4 Laboratory Service, 5 2015 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 10.1126/sciadv.1500183 R E S E A R C H A R T I C L E
  23. 23. M I C R O B I A L E C O L O G Y The microbiome of uncontacted Amerindians Jose C. Clemente,1,2 * Erica C. Pehrsson,3 * Martin J. Blaser,4,5 Kuldip Sandhu,5† Zhan Gao,5 Bin Wang,3 Magda Magris,6 Glida Hidalgo,6 Monica Contreras,7 Óscar Noya-Alarcón,6 Orlana Lander,8 Jeremy McDonald,9 Mike Cox,9 Jens Walter,10‡ Phaik Lyn Oh,10 Jean F. Ruiz,11 Selena Rodriguez,11 Nan Shen,1 Se Jin Song,12 Jessica Metcalf,12 Rob Knight,12,13§ Gautam Dantas,3,14 M. Gloria Dominguez-Bello5,7,11¶ Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a micro- biome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that western- ization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mo- bilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need for extensive characterization of the function of the microbiome and resistome in remote nonwesternized popula- tions before globalization of modern practices affects potentially beneficial bacteria harbored in the human body. INTRODUCTION Host-microbial interactions are important determinants of host phys- iology, including immune responses, metabolic homeostasis, and be- havior (1–4). Microbiota transplantation can transfer phenotypes such as nutritional status from donor to recipient (5, 6), indicating that al- tered microbial communities can therefore cause, as well as result from, altered physiological states. Despite increasing evidence that the micro- biome has important roles in human health, we do not yet know the extent to which the human microbiome has changed during the adop- tion of life-styles associated with westernization. Here, we described the microbiome from Yanomami subjects in the Amazon with no previous report of contact with non-Yanomami. The Yanomami were originally mountain people who were first contacted in the mid-1960s, and who continue to live seminomadic hunter-gatherer life-styles in the Amazon jungle. In Venezuela, they inhabit a region protected from development, and many still inhabit uncharted villages in the vast mountainous Yanomami territory (7). These remote populations of hunter-gatherers have life-styles similar to those of our human ancestors, and are unex- posed to modern practices known to exert antimicrobial effects. For instance, pharmacologic-dose antibiotic exposure is nearly ubiq- uitous worldwide, and all human microbiota studied to date, remote or industrialized, harbor diverse antibiotic resistance (AR) genes (8, 9). Al- though AR genes have been computationally predicted in ancient oral microbiota (10), functional resistance from the preantibiotic era re- mains largely uncharacterized. These subjects from an uncontacted community therefore represent a unique proxy for the preantibiotic era human resistome. Here, we characterized the microbiome and resis- tome of these subjects, and compared them to those of othernon-isolated populations. Samples of the oral cavity (n = 28), forearm skin (n = 28), and feces (n = 12) were obtained from 34 of the 54 villagers (table S1) at thetimeofthefirstmedicalexpeditiontoanisolated,previouslyuncharted village in the High Orinoco state of Venezuela. The age of the subjects was between 4 and 50 years, as estimated by Yanomami health workers. 1 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 2 Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 3 Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. 4 Laboratory Service, 5 2015 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 10.1126/sciadv.1500183 R E S E A R C H A R T I C L E
  24. 24. The importance of wrong • Our goal is to generate robust knowledge to advance science • “I was wrong” should not be taboo • Respond quickly, admit error, make correction
  25. 25. To sum up • You’re in the business of generating and disseminating knowledge • World class outputs stand the test of time and make a difference • Focus on generating and disseminating robust knowledge • You make it world class!
  26. 26. A new reward culture? YOU can make it happen!

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