How to publish your manuscript (II)

1. How to publish your manuscript (II) Kent HayGlass Alan Sher October 11, 2006

2. Jan 06 • Drs. Kent HayGlass, Monther Al-Alwan, Anita Kozyrskyj and Renée DouvilleHow to review/write a scientific paperDownload all four Powerpoint presentations from this seminar in one file >> • UM Immunology website: Reference and Research tools

3. “Mimification” • Essentials of writing biomedical research papers 1999 • M.Zeiger – NJM Library or bookstore • ~$C65 at Indigo or Amazon. • Best investment you’ll make if you stay in science! • Website has synposis

4. How –and why--to publish your manuscript • Dr Alan Sher, Head, Laboratory of Parasitic Diseases, NIH Immunity PNAS Science J Immunology Nature Immunology J Clin Invest J Exp Med JBC …

5. A real bad crude analogy Productivity + Professional advancement

6. In case of postdocs and students: Major “tangible” criteria used in hiring of young scientists and major factor in obtaining first funding from grant agencies

7. Research without publication is like a …….. It don’t exist unless heard (published)!

8. The really good (non-material) benefits from writing up your work • Forces you to focus and carefully analyze what you are doing thereby saving wasted bench work and time. • Forces you to articulate your ideas and put in context of your field. • Ensures you are current with the literature. • Through review process, gives you valuable and detailed (although frequently painful) criticism of your work that you are unlikely to get from oral presentations.

9. What’s Important in Your Publication Record • Quantity vs Quality?? • Nothing beats high quality/highly original papers in good journals. • But few of us can pull this off consistently. • Instead when there are no great breakthroughs-- need to write-up findings we have to maintain evidence of productivity and to mark our involvement in work on subject (i.e. “stake out territory”).

10. What’s Important in Your Publication Record.. Cont. • Boutique (Science/Nature) vs trade journals (JBC, JID,JI).? A highly cited paper in latter counts more than a poorly cited paper in former. • Review articles? – generally a waste of time for younger scientists. Do when you have accumulated expertise and a list of your own publications in field.Useful as a freebie but don’t get distracted. • First authorship? - Critical at your stage but some middle author papers also help as evidence of good team work ethic and collegiality. Enhance productivity. • Collaborations: Risks and benefits in your portfolio of project/time allotment. .

11. When is the appropriate time to write up your work? • Must have reproduciblenew observation where you make it explicitly clear why “new and important”. Ideally, should not be a “me too” description. • If hot competitive new finding may need to rush publish in brief format without “mechanism”. • Ideally should have thorough analysis of question with strong evidence for mechanism involved. • However, if clear cut explanation of original observations cannot be obtained in reasonable time “cut bait” and package story emphasing as focus the most novel aspects of your data. Pitch to appropriate journal.

12. When is the appropriate time to write up your work? Cont. • Keep paper focused on topic . Combining several incomplete stories doesn’t necessarily make a complete one. • No laundry lists. Keep story in mind. • Don’t sit on data! You will lose both focus and interest and your work will never get published.

13. Writing up your papers after you’ve moved on to your next position

14. Do it now • Makes thesis writing MUCH easier • It counts more for your future career than does your thesis.

15. How to begin • Assemble data items that will go together, brainstorm best figure formats/tables • If possible run through story in seminar, meeting presentation or with colleagues. • Ask ? “Do you guys think I have a story now”?

16. The Prospectus • Before undertaking all this, make up a one page prospectus on “Why bother? What done? What seen? Fig 1,2,3 with legend/conclusion, Take home message, Significance/Novelty. • Roadblocks • Verify with your friends and supervisor ! • Use for experimental planning: Grocery store analogy • Sample handouts from Ruey Su and Renee Douville

17. What parts of paper should be written first? Materials and Methods References Discussion Results Title Running Title Abstract Introduction Figure legends Title Abstract Results Figure Legends Introduction Discussion Materials and Methods References (Running Title)

18. Abstract and Title • The only thing read by 90% of your readers. • Reviewer’s first and often final impression of paper is made here. • Title must be clear and crisp and emphasize most novel aspect of your data . • Avoid descriptive titles e.g “Studies on lymphatic filariasis in mongolian jirds” • A declarative sentence is best if possible. • Abstract should provide BRIEF rationale, describe key experimental findings, major conclusion and significance

19. Exercise: Write a title, running title (6 words max) and abstract (200 words max) for a paper about this data • BALB/c male and female mice caged together given increasing % of gin in their water bottles. • As dose escalates, loss in motor co-ordination, increased aggressiveness, mating behavior observed which peak at moderate % (22-27) of gin administered. • At higher doses liver damage and mortality seen. • SJL/mice in contrast show no increase in mating, aggression or loss in co-ordination, after gin administration but also die at high dose. • SJL mice have higher levels of alcohol dehydrogenase (ADH) than BALB/c mice. • BALB/c mice overexpressing an ADH transgene are protected against gin induced behavioral effects but not mortality. ADH deficient (KO) SJL mice are highly susceptible to all gin effects. + = ???

20. Organizing Results Section • Introduce key observation, fill in details, and than try to end on most revealing mechanistic data you have rather than weak descriptive point. • Provide clear cut headings to each section that summarize its key point and make statement: “SJL mice fail to display gin induced behavioral effects.”(declarative) instead of “ Effects of gin administration in SJL mice”. • Keep tense consistent. Use present tense for statement of fact or mechanism. “ When administered gin, BALB/c mice displayed profound behavioral abnormalities and mortality at higher doses. These observations demonstrated that mice of this inbred strain are highly susceptible to this intoxicant.”(implies generalizability and capacity of data to predict future)

21. Organizing Results Section, cont • Avoid long paragraphs. If experiments described are detailed, provide concluding summary statement that will dovetail with next section heading. “The above observations indicated that upon ingestion of gin BALB/c mice exhibit many of the behavioral effects commonly observed in humans receiving the same intoxicant.

22. Writing Figure Legends • Not trivial ! • Rules? • Be sure to make title distinct from section title. One idea is to be more descriptive: “Effects of gin on behavior and mortality of BALB/c mice” • If multipanel figure (e.g Fig1, A,B,C.): Put description of common elements of expts firstfollowed by specifics of each panel. “ Gin was administered to groups of mice (n=5) at varying doses over a 60 d period”. Aggressive encounters (A), hanky-panky (B) and mortality (C) were then monitored using published methods”.

23. Writing Figure Legends, cont • Clearly indicate number of determinations per point, number of mice or patients analyzed, and number of experiments performed and statistics. Indicate if data are averaged from or are representative of multiple experiments.(Nature stat adequacy questionaire on web) “The experiment shown is representative of 3 performed” • Ok to refer to previous figure to simplify. “ SLJ/J mice were administered gin and examined for behavioral effects and mortality as in Fig1”

24. Writing Introductions • Include relevant background and cite key references. Avoid lengthy discussion of previous findings. FOCUS • Be sure to clearly state rationale. • End with brief summary of findings and implications but do not repeat Abstract. • Try to limit to 3 ds pages maximum.

25. Crafting Discussions • Do not simply re-iterate results but good idea to begin with summary of key NOVEL conclusions. E.g.: “The results presented in this paper from studies on a murine model clearly demonstrate that the behavioral consequences of alcohol consumption are under genetic control.” • Then begin to discuss interpretations of data highlighting any important complexities and comparing with previous findings. You need not reconcile with every paper in PubMed • End with major implications of data for field. E.g.: “These data suggest that individuals with certain genetic backgrounds may be more prone to alcoholism”. • Avoid “throw away” comments like “ This question is currently under study in our laboratory”.Caution with Future studies… • Most Discussions peter out by 5-6 pages. Try to avoid anything longer. • End with clear summary paragraph emphasizing take home message .

26. Materials and Methods: easy! • Begin by listing (outlining) subheadings. • Start with most general topics.: “Mice and experimental infections” “Reagents and antibodies. • Proceed with specific procedures in chronological order as they appear in Results: “Measurement of cytokine mRNA levels”. • End with Statistics section. • Golden rule: Reader should be able to reproduce experiment with information provided or cited from previous publication

27. Manuscript Rebuttals:Politics / Manners • Very few manuscripts are accepted without criticism. Don’t take comments personally or become hostile. • Understand the reviewer’s mentality. She/he is doing this as service (often late at night) and will not respond favorably to a knee-jerk antagonistic reply. • Be polite and open by thanking the editors for their helpful and constructive comments, etc.. • If they misunderstood it’s our communication skills at fault. • Be modest. Admit your mistakes. If reviewer has missed point say that you will now attempt to explain better.

28. Manuscript Rebuttals:Organization • Decide ahead of time what new experiments will be required and what criticisms you can simply address in text. Get a second opinion. • When necessary experiments are done, write rebuttal letter first and then make changes to manuscript. • After opening thank-you’s, provide summary of your plans for revision. “ In response to the reviewers criticisms, we have thoroughly revised our manuscript, providing new data on gin vs vodka effects and tempering our interpretaions about the relevance of our data to human alcoholism.”

29. Manuscript Rebuttals:Execution • Important: List response in point by point fashion briefly summarizing criticism so that editor can refer back to review: “ This reviewer asks whether we have controlled for variations in the proof of the gin employed” • Clearly indicate the changes made by underlining or bolding the changes made. This is what reviewers/editors want to see: “In response to the reviewer’s comment, we now state in the Materials and Methods that the same proof of gin was used throughout.” • If you choose not provide requested information state why: “We have decided not to state the proof of gin employed as this figure is well known to all drinkers and is quoted in our previous papers.” You don’t need to respond to everything. • End with positive statement: “ We hope that our revised manuscript has now addressed the major concerns of reviewers and is now suitable for publication in Alcoholism Research.”

30. Titles • ADH: a critical regulator of amoral behavior • alcohol dehydrogenase protects mammals from alcohol induced disinhibition, but not mortality • Alcohol Induced Behavioral And Motor Effects Are Obliterated In Mice Overexpressing Alcohol Dehydrogenase • Resistance to alcohol-induced behavioral effects is associated with higher alcohol dehydrogenase levels in the liver. • High level of Expression of the Enzyme Alcohol Dehydrogenase protects from Alcohol-Induced Behavior Deviation but not Mortality • Evidence for a link between alcohol dehydrogenase levels and gin induced behavior in SJL and BALB/c mice.

31. Titles-2 • Alcohol dehydrogenase regulates alcohol-induced behavioral abnormality but not mortality • Decreased alcohol dehydrogenase gene expression leads to unsavory behaviors in Balb/C mice • Alcohol dehydrogenase controls toxin-dependent behavior • Alcool dehydrogenase protects mice against alcool effects on behavior and motor co-ordination. • Alcohol Dehydrogenase Rescues Motor and Behavioral Impairment in a Murine Model of Intoxication

32. Running titles • ADH Mitigates Behavioral Effects of Intoxication • Alcool dehydrogenase protects against alcool effects. • Alcohol dehydrogense protects from gin induced misbehavior • Unsavory behaviors correspond to ADH levels • ADH controls alcohol-induced behavioral effects • Link between ADH and gin behavior

33. Running Titles-2 • alcohol dehydrogenase and alcohol-induced mortality • Alcohol dehydrogenase and drunk behavior • Alcohol dehydrogenase levels regulate alcoholic behavior • ADH acts on alcohol induced disinhibition

34. Questions? Experiences to share? Different perspectives?