what are world class scientific outputs?

What are world class scientific outputs?

Sophien Kamoun

http:KamounLab.net @KamounLab

Why am I a scientist?

My inspiration…

“Je cherche à comprendre” “I seek to understand”

Jacques Monod

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

…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

CommunicationWe must communicate our discoveries to other scientists, the government, the public etc. !Otherwise the impact will be quasi-nil

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• An archived document that enables others to be inspired and build on your research (or dispute it)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!

How do we recognise world class publications?

confirmation influence / impact

How to evaluate papers?Judge publications on their own merit Don’t use journals as proxy Article-level metrics

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.”

Death to the impact factorMisused and abused Crude statistically flawed metric Skewed by few highly cited papers

The weakening relationship between the Impact Factor and papers’ citations in the digital age George A. Lozano, Vincent Lariviere, Yves Gingras

data were split into 1902–1958, 1959–1990, and 1991–2009. For medical and natural sciences (Figure 1), there wasan increase of the correlation between IF and paper citationrates from 1902 until the end of the 1990s. The strength ofthe relationship between IF and citations did not increasesteadily throughout the 20th century. Two dips occurredafter the two World Wars, likely as a result of changes in theresearch system. More interestingly and in contrast to thegeneral pattern throughout most of the 20th century, sincescientific information began to be disseminated electroni-

cally, around 1990, the relationship between the IF andcitation rates has been weakening.

The same analyses were carried out with two disciplinesthought to be at opposite ends of the spectrum of howquickly they made the transition into the electronic domain:physics (Figure 2) and social sciences (Figure 3). Given thesmaller sample size, the variation of the r2 values between IFand papers’ citation rates is larger, but in both cases therewas a decrease during the last two decades. Although thedecrease is not significantly different in the two disciplines,

y = 0.0011x - 1.9418r2 = 0.4666

y = 0.003x - 5.7759r2 = 0.579

y = -0.0049x + 9.9863r2 = 0.4788

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FIG. 1. Coefficient of determination (r2) between the impact factor of journals and the two-year citation rate of their papers from 1902 to 2009, for allnatural and medical sciences journals.

y = 0.0023x - 4.2978r2 = 0.7291

y = -0.0026x + 5.4626r2 = 0.5712

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1900 1920 1940 1960 1980 2000 2020

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FIG. 2. Coefficient of determination (r2) between the impact factor of physics journals and the two-year citation rate of their papers from 1902 to 2009.

2142 JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY—November 2012DOI: 10.1002/asi

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

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

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

• 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

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

• 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 UsingArsenic Instead of PhosphorusFelisa 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, andphosphorus. Although these six elements make up nucleic acids, proteins, and lipids and thusthe bulk of living matter, it is theoretically possible that some other elements in the periodictable could serve the same functions. Here, we describe a bacterium, strain GFAJ-1 of theHalomonadaceae, isolated from Mono Lake, California, that is able to substitute arsenic forphosphorus to sustain its growth. Our data show evidence for arsenate in macromolecules thatnormally contain phosphate, most notably nucleic acids and proteins. Exchange of one of themajor bio-elements may have profound evolutionary and geochemical importance.

Biological dependence on the six majornutrient 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 intrace quantities that serve critical cellular func-tions, such as enzyme co-factors (1). There aremany cases of these trace elements substitutingfor one another. A few examples include the sub-stitution of tungsten for molybdenum and cad-mium for zinc in some enzyme families (2, 3) andcopper for iron as an oxygen-carrier in some ar-thropods andmollusks (4). In these examples andothers, the trace elements that interchange sharechemical similarities that facilitate the swap. How-ever, there are no prior reports of substitutionsfor any of the six major elements essential forlife. Here, we present evidence that arsenic cansubstitute for phosphorus in the biomolecules ofa naturally occurring bacterium.

Arsenic (As) is a chemical analog of P, whichlies directly below P on the periodic table. Arsenicpossesses a similar atomic radius, as well as nearidentical electronegativity to P (5). The most com-mon form of P in biology is phosphate (PO4

3–),which behaves similarly to arsenate (AsO4

3–) overthe range of biologically relevant pH and redoxgradients (6). The physicochemical similarity be-tween AsO4

3– and PO43– contributes to the bio-

logical toxicity of AsO43– because metabolic

pathways intended for PO43– cannot distinguish

between the two molecules (7) and AsO43– may

be incorporated into some early steps in the path-ways [(6) and references therein]. However, it isthought that downstream metabolic processes aregenerally not compatible with As-incorporatingmolecules because of differences in the reactiv-ities of P and As compounds (8). These down-

stream biochemical pathways may require themore chemically stable P-based metabolites; thelifetimes of more easily hydrolyzed As-bearinganalogs are thought to be too short. However,given the similarities of As and P—and by anal-ogywith trace element substitutions—we hypoth-esized that AsO4

3– could specifically substitutefor PO4

3– in an organism possessing mechanismsto cope with the inherent instability of AsO4

3–

compounds (6). Here, we experimentally testedthis hypothesis by using AsO4

3–, combined withno 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 andalkaline water body with high dissolved arsenicconcentrations [200 mMon average (9)].We usedlake sediments as inocula into an aerobic definedartificial medium at pH 9.8 (10, 11) containing10 mM glucose, vitamins, and trace metals but noadded PO4

3– or any additional complex organicsupplements (such as yeast extract or peptone),with a regimen of increasing AsO4

3– additionsinitially spanning the range from 100 mMto 5mM.These enrichments were taken through manydecimal-dilution transfers, greatly reducing anypotential carryover of autochthonous phosphorus

1NASA Astrobiology Institute, USA. 2U.S. Geological Survey,Menlo Park, CA 94025, USA. 3School of Earth and SpaceExploration, Arizona State University, Tempe, AZ 85287, USA.4Lawrence Livermore National Laboratory, Livermore, CA 94551,USA. 5Department of Biological Sciences, Duquesne University,Pittsburgh, PA 15282, USA. 6Stanford Synchrotron RadiationLightsource, Menlo Park, CA 94025, USA. 7BEYOND: Centerfor Fundamental Concepts in Science, Arizona State University,Tempe, AZ 85287, USA. 8Department of Chemistry and Bio-chemistry, Arizona State University, Tempe, AZ 85287, USA.

*To whom correspondence should be addressed. E-mail:[email protected]

5µm

5µm

1µm

C

D

E

A

B

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5 x 106

5 x 107

5 x 108

cells

ml-1

0 120 240 360 480Time (h)

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Fig. 1. Growth and electron microscopy of strain GFAJ-1. (A and B) Growth curves of GFAJ-1 grown onthe defined synthetic medium amended with either 1.5 mM PO4

3– (solid circles), 40 mM AsO43– (solid

squares), or neither PO43– nor AsO4

3– (open triangles). Cell growth was monitored both by an increase in(A) optical density and (B) cell numbers of the cultures. Symbols represent the mean T SD of (A) n = 6experimental and n = 2 controls and (B) n = 3 experimental and n = 1 control. This was a singleexperiment with six replicates; however, material was conserved to extend the duration of the experimentto allow material for cell-counting samples. (C and D) Scanning electron micrographs of strain GFAJ-1under two conditions, (C) +As/–P and (D) –As/+P. (E) Transmission electron micrography of +As/–P GFAJ-1showed internal vacuole-like structures. Scale bars are as indicated in the figure (11).

RESEARCHARTICLE

www.sciencemag.org SCIENCE VOL 332 3 JUNE 2011 1163

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ARTICLEdoi:10.1038/nature12968

Stimulus-triggered fate conversion ofsomatic cells into pluripotencyHaruko 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 externalstimuli 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 germlinetransmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, ourfindings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependentmanner by strong environmental cues.

In the canalization view of Waddington’s epigenetic landscape, fatesof somatic cells are progressively determined as cellular differentiationproceeds, like going downhill. It is generally believed that reversal ofdifferentiated status requires artificial physical or genetic manipulationof nuclear function such as nuclear transfer1,2 or the introduction ofmultiple transcription factors3. Here we investigated the question ofwhether somatic cells can undergo nuclear reprogramming simply inresponse to external triggers without direct nuclear manipulation. Thistype of situation is known to occur in plants—drastic environmentalchanges can convert mature somatic cells (for example, dissociated carrotcells) into immature blastema cells, from which a whole plant structure,including stalks and roots, develops in the presence of auxins4. A chal-lenging question is whether animal somatic cells have a similar potentialthat emerges under special conditions. Over the past decade, the pres-ence of pluripotent cells (or closely relevant cell types) in adult tissueshas been a matter of debate, for which conflicting conclusions havebeen reported by various groups5–11. However, no study so far has proventhat such pluripotent cells can arise from differentiated somatic cells.

Haematopoietic cells positive for CD45 (leukocyte common antigen) aretypical lineage-committed somatic cells that never express pluripotency-related markers such as Oct4 unless they are reprogrammed12,13. Wetherefore addressed the question of whether splenic CD451 cells couldacquire pluripotency by drastic changes in their external environmentsuch as those caused by simple chemical perturbations.

Low pH triggers fate conversion in somatic cellsCD451 cells were sorted by fluorescence-activated cell sorting (FACS)from the lymphocyte fraction of postnatal spleens (1-week old) ofC57BL/6 mice carrying an Oct4-gfp transgene14, and were exposedto various types of strong, transient, physical and chemical stimuli(described below). We examined these cells for activation of the Oct4promoter after culture for several days in suspension using DMEM/F12medium supplemented with leukaemia inhibitory factor (LIF) and B27

(hereafter called LIF1B27 medium). Among the various perturbations,we were particularly interested in low-pH perturbations for two reasons.First, as shown below, low-pH treatment turned out to be most effectivefor the induction of Oct4. Second, classical experimental embryologyhas shown that a transient low-pH treatment under ‘sublethal’ conditionscan alter the differentiation status of tissues. Spontaneous neural conver-sion from salamander animal caps by soaking the tissues in citrate-basedacidic medium below pH 6.0 has been demonstrated previously15–17.

Without exposure to the stimuli, none of the cells sorted with CD45expressed Oct4-GFP regardless of the culture period in LIF1B27 medium.In contrast, a 30-min treatment with low-pH medium (25-min incuba-tion followed by 5-min centrifugation; Fig. 1a; the most effective rangewas pH 5.4–5.8; Extended Data Fig. 1a) caused the emergence of sub-stantial numbers of spherical clusters that expressed Oct4-GFP in day-7culture (Fig. 1b). Substantial numbers of GFP1 cells appeared in all casesperformed with neonatal splenic cells (n 5 30 experiments). The emer-gence of Oct4-GFP1 cells at the expense of CD451 cells was also observedby flow cytometry (Fig. 1c, top, and Extended Data Fig. 1b, c). We nextfractionated CD451 cells into populations positive and negative forCD90 (T cells), CD19 (B cells) and CD34 (haematopoietic progenitors18),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 onday 7), except for CD341 haematopoietic progenitors19, which rarelyproduced Oct4-GFP1 cells (,2%; Extended Data Fig. 1d).

Among maintenance media for pluripotent cells20, the appearanceof Oct4-GFP1 cells was most efficient in LIF1B27 medium, and didnot occur in mouse epiblast-derived stem-cell (EpiSC) medium21,22

(Extended Data Fig. 1e). The presence or absence of LIF during days0–2 did not substantially affect the frequency of Oct4-GFP1 cell gen-eration on day 7 (Extended Data Fig. 1f), whereas the addition of LIFduring days 4–7 was not sufficient, indicating that LIF dependencystarted during days 2–4.

1Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 2Laboratory for Cellular Reprogramming,RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 3Laboratory for Genomic Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 4Laboratory forOrganogenesis and Neurogenesis, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 5Department of Pathology, Irwin Army Community Hospital, Fort Riley, Kansas 66442, USA.6Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 7Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s MedicalUniversity, Tokyo 162-8666, Japan. {Present address: Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.

3 0 J A N U A R Y 2 0 1 4 | V O L 5 0 5 | N A T U R E | 6 4 1

Macmillan Publishers Limited. All rights reserved©2014

RETRACTED

#arseniclife - what happened?!• Postpublication peer review (PPPR) • Addressed flaws of pre-pub peer review • Social media and blogs

MICROB IAL ECOLOGY

The microbiome of uncontacted AmerindiansJose 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 decreasemicrobial survival and transmission, or on traditional societies that are currently in transition to westernization. Wecharacterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated YanomamiAmerindian 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 theirisolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure toantibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that conferresistance 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 thehuman 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 needfor 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 suchas 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 theextent to which the human microbiome has changed during the adop-tion of life-styles associated with westernization. Here, we described themicrobiome from Yanomami subjects in the Amazon with no previousreport of contact with non-Yanomami. The Yanomami were originallymountain people who were first contacted in the mid-1960s, and whocontinue 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 mountainousYanomami territory (7). These remote populations of hunter-gatherershave 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 humanmicrobiota studied to date, remote orindustrialized, harbor diverse antibiotic resistance (AR) genes (8, 9). Al-though AR genes have been computationally predicted in ancient oralmicrobiota (10), functional resistance from the preantibiotic era re-mains largely uncharacterized. These subjects from an uncontactedcommunity therefore represent a unique proxy for the preantibioticera human resistome. Here, we characterized the microbiome and resis-tomeof these subjects, and compared them to those of other non-isolatedpopulations. 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) atthe timeof the firstmedical expedition to an isolated, previously unchartedvillage in the High Orinoco state of Venezuela. The age of the subjectswas between 4 and 50 years, as estimated by Yanomami health workers.

RESULTS

Unprecedented high bacterial and functional diversity in themicrobiome of uncontacted AmerindiansWe sequenced the V4 region of the 16S rRNA gene from fecal, oral,and skin samples and compared these data with those from previousstudies (11, 12). The microbiome of the uncontacted Amerindians ex-hibited the highest diversity ever reported in any human group. Di-versity in feces and skin, but not in the mouth, was significantly higherin Yanomami than in U.S. subjects (Fig. 1, A, E, and I). Noticeably,fecal diversity was even higher than in the semitransculturatedGuahibo Amerindians and Malawians [analysis of variance (ANOVA)

1Department of Genetics and Genomic Sciences, Icahn School of Medicine at MountSinai, New York, NY 10029, USA. 2Immunology Institute, Icahn School of Medicine atMount Sinai, New York, NY 10029, USA. 3Center for Genome Sciences & Systems Biology,Washington University School of Medicine, St. Louis, MO 63108, USA. 4Laboratory Service,VA Medical Center, New York, NY 10010, USA. 5New York University School of Medicine,New York, NY 10016, USA. 6Amazonic Center for Research and Control of Tropical Diseases(CAICET), Puerto Ayacucho 7101, Venezuela. 7Venezuelan Institute for Scientific Research,Caracas 1020-A, Venezuela. 8Sección de Ecología Parasitaria, Instituto de Medicina Tropical,Universidad Central de Venezuela, Caracas 1051, Venezuela. 9Anaerobe Systems, MorganHill, CA 95037, USA. 10Department of Food Science and Technology, University of Nebraska,Lincoln, NE 68583, USA. 11Department of Biology, University of Puerto Rico, Rio Piedras00931, Puerto Rico. 12Department of Chemistry and Biochemistry, University of Colorado,Boulder, CO 80309, USA. 13Howard Hughes Medical Institute, University of Colorado,Boulder, CO 80309, USA. 14Department of Pathology and Immunology, Washington Uni-versity School of Medicine, St. Louis, MO 63110, USA.*These authors contributed equally to this work.†Deceased.‡Present address: Department of Biological Sciences and of Agricultural, Food, andNutritional Science, University of Alberta, Alberta, Edmonton T6G 2R3, Canada.§Present address: Departments of Pediatrics and Computer Science & Engineering,University of California at San Diego, La Jolla, CA 92093, USA.¶Corresponding author. E-mail: [email protected]

2015 © The Authors, some rights reserved;exclusive licensee American Association forthe Advancement of Science. Distributedunder a Creative Commons AttributionNonCommercial License 4.0 (CC BY-NC).10.1126/sciadv.1500183

R E S EARCH ART I C L E

Clemente et al. Sci. Adv. 2015;1:e1500183 17 April 2015 1 of 12

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

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!

A new reward culture? YOU can make it happen!

what are world class scientific outputs?

Science

journals papers

papers citations

web of science

power of science

impact factor of journals

cited zombie papers

retracted papers

science writing forces