Manuscript submissions and revisions. The professional editors The editors are usually PhD in this field (many of them have postdoc training in good labs)

Manuscript submissions and revisions

The professional editors

• The editors are usually PhD in this field (many of them have postdoc training in good labs).

• They read thousands of manuscripts in their career.

• Hundreds of manuscripts are submitted to them every week.

• They spend ~20-30 minutes for a new manuscript .

• Why they want to publish your work?

Editorial board

• A number of regular referees who are responsible for reviewing and evaluating submitted papers.

• Usually the well-established scientists in the filed.

• Referees may also advise the editor on the development of the journal's thematic scope and focus.

• External reviewer will be suggest by editorial board when no appropriate expertise to make professional comments on a particular paper.

1. Novelty

2. Interest

3. Clarity

4. Evidence

What editors are looking for

Manuscript reviewing process

Cover letter

• First impression to editor (who has only 20-30 minutes to decide whether your paper deserve to be reviewed).

• 1st section: title + article type

• 2nd section: Key findings and significance of your study (not your abstract).

• 3rd section: conflict interests

Dear Editor,Attached is our manuscript entitled “Arctic mutation: At the tip of the amyloid

iceberg”. Please consider it for publication as a Brief Communication in Nature Medicine.

Our paper describes the first transgenic mouse model of the so-called Arctic mutation, major findings….

Our preliminary characterization of the new models reveals that the Arctic mutation causes a highly aggressive cerebral fibrillosis. Importance of your findings …... We therefore consider the generation of these models a significant breakthrough that will be of interest to a significant proportion of your readership.

We decided to submit a brief description of these models at this time because we have become aware of the fact that two other groups (Lars Lannfelt and associates, and Manfred Windisch and associates) have independently established, but not yet published, similar models. We are therefore eager to publish our findings as soon as possible and hope that you will consider the rapid communication of our data to be of interest also to the journal and the scientific community in general.

We would like to request that Drs. David Teplow, Lars Nilsson, and Mary Jo LaDu not be asked to review this manuscript.

We look forward to your response.Sincerely,Lennart Mucke, M.D.

Exclude/suggest reviewers

• Know your friends and enemies • Editor usually don’t send to person who publish with you

before.• Usually no more than 3.• Not all the journal accept this list.• Editor use as reference, not always follow the list.


After long waiting period ……

• Return without review (24 hours to a week)• Send out for review (3 wks to 3 months)

• Don’t take vacation. Try to generate more data during this time!!!

Reasons for early rejection (without review)

• Limited interest to the editor/journal

• Novelty and significance are not immediately evident or sufficiently well-justified

• Failure to meet submission requirements

• Incomplete coverage of literature

• Unacceptably poor English

Options?

(i) Move on to the next journal the second day.

(ii) If you have a GOOD case, write to the editor with a calm, clear and fact-centred rebuttal.

(iii) If not satisfied with the editor's response to your rebuttal, write to the Editor-in chief (good luck).

The Reviewers

• Usually 1-3 experts in the related field.

• Some reviewers spend only 15 minutes reading your paper, or ask their students to review for them.

• Your key words may also determine your reviewers.

• Think about why the reviewers made such comments.


Possible outcomes

1. Manuscript may be accepted without any changes. Lucky and rare (go buy a lottery ticket!).

2. May be accepted with suggestions for minor revisions. Still lucky. Quickly make changes, and return the revised manuscript.

On p. 6, par. 2, the phrase "was caused by" should be changed to "correlated with". On p. 7, par. 2, the word "seemly" (line 3) should be changed to "seemingly".

Good sign

• ”This work presents a very interesting and original approach”

• ”The work is interesting and publishable”

• ”The referees found the manuscript very interesting and suggested only some minor revisions”

• ”This excellent paper should be published as soon as possible”

• ”This paper is a most valuable contribution that deserves to be published”

Editors can change their mind anytime

• Make sure the decision is final before party!!• Make any required modification IMMEDIATELY.

Possible outcomes

3. Rejection with the opportunity to make major revisions.

4. Absolute rejection.

How rejected is rejected?

“it’s not a real rejection” rejection

The paper is not acceptable in its present form:• Means that the manuscript is likely to be accepted,

subject to revisions.• The journal may be interested in your study, but will not

commit itself until the editors and reviewers see the added data or corrections.

• This type of rejection letter will usually say that this manuscript would need to be received within a reasonable period of time (usually 1-6 months) to be considered as a revision.

“there are things between us” rejection

The study is interesting but is technically flawed• Editors like it, but reviewers have serious reservations

about some of the data.

• May require showing data that you omitted, or repeat experiment in different ways.

• If you can address these issues, the paper may be reconsidered.

“we like you, but not love you yet” rejection

The study is interesting but too preliminary• The editor indicates that the manuscript is interesting, but

is not a complete story.

• An opening for a revised manuscript. The main question is whether you actually have the data.

• Were you saving the data for another manuscript, perhaps with other authors, or is this the first step in a long series of studies?

• Will the complete story take five more years of work?

“everything that’s new is old ” rejection

The study is incremental

• Study repeats experiments in a slightly different way or different system with the same outcome.

• Reviewer or editor can’t find anything interesting.

• Did you research the literature thoroughly to find out if your study is an original contribution?

“we’re just not that into you” rejection

The paper did not get a high enough priority• Priorities are based on the perceived interests of their

readership.

• If the rejection was editorial, then the manuscript was viewed as not being a likely candidate for acceptance even if reviewed favorably.

•This paper is not “news-worthy” for some high impact journals.

“You are a nice guy” rejection

The work is more appropriate for a specialized journal

• The manuscript may only be interested to specialized readers.

• A revision is unlikely to be considered.

• The reviewers’ comments will help you prepare the manuscript for another journal.

• Some editorial can transfer your manuscript to branch journal without further review.

The data are not convincing• The manuscript lacks important controls

• You have not provided enough compelling data to convince the reviewer of your conclusions.

• Did you do the experiment sufficient times to get statistical validity?

• Is the quality of the data (gels, photographs, scatter in the data points) good enough to be convincing?

“just go away” rejection

“just go away” rejection

The study is descriptive• The death knell of reviews!

• All research describes observations.

• As a criticism the reviewers are indicating that the study reads as a collection of data that does not come together into a clear hypothesis-driven study.

• If that’s not the case, re-write the paper and emphasize your novelty.

Possible response for rejection:

first the tears then the anger

General Rules On Dealing With Rejection

Rule 1. Call your best friends. Get drunk.

Rule 2. Send the reviews to friends and ask for their opinion.

Rule 3. Hide the manuscript and reviews for 1 or 2 days.

Rule 4. When the hurt has gone, deal with the criticisms and /or resubmit to another journal.

Rule 5. Don’t take it personal.

Nature received >9,000 manuscripts at 2003 and rejected about 95% of biomedical papers. Development, a quality specialist journal, now rejects roughly 70% of paper.


Revision

– You received an invitation to revise the paper because it might contain good idea, but not publishable quality yet.

– There usually a time limit for resubmission, try your best to finish in time.

– If you plan to resubmit the paper without revision (usually request for another reviewer), let the editorial office know of your intention (via e-mail/phone call).

– Sloppy, rough revisions will surely result in rejection.

Be optimistic and get excited

Don't blow it. Take the time to do a good job. The goal is to ensure

acceptance, not to minimize the effort. Do not save your effort. Go the extra mile. You have a

chance (about 50%).

Write a detailed response to individual referees

• Take every comment of the referee seriously. • In a note to be transmitted to the referee, first thank

him or her. • Number all relevant comments and respond to those

(explain what you did in the revised paper). • Indicate that you are doing everything possible and

more. • If you cannot accommodate the demands, offer

explanations why they are beyond the scope of the paper or why it is not possible at the time.

Dear Dr. Grossman,Thank you for the reviews of our manuscript entitled “Arctic Mutation: At the tip of amyloid iceberg” (NMED-BC22630). In accordance with your suggestion, the title of the manuscript has been made more descriptive: “Aggressive Brain Amyloidosis in Transgenic Mice Expressing Human Amyloid Peptides with the Arctic Mutation.” We have carefully considered the reviewers’ helpful comments and revised the manuscript accordingly. Our point-by-point response is enclosed.We hope your will find our revised manuscript acceptable for publication in Nature Medicine.Sincerely,Lennart Mucke, M.D.

Letter to editor

Dear Referees:Thank you for the reviews of our manuscript entitled “Arctic Mutation: At the

tip of amyloid iceberg” (NMED-BC22630). The title of this manuscript changes to “Aggressive Brain Amyloidosis in Transgenic Mice Expressing Human Amyloid Peptides with the Arctic Mutation”.

We have considered the comments of the reviewers and we have revised the manuscript accordingly. Our detailed responses to the reviewers’ comments are enclosed. The original comments of each reviewer are in italics. Our responses follow each of the comments in regular style.

We hope the revised manuscript is now acceptable for publication in Nature Medicine.

Yours truly,Lennart Mucke

Letter to reviewers

In general, the work seems to be carefully designed and executed.We thank the reviewer for this evaluation.

The main merit of this study is to provide clear evidence for an involvement of the PLA2 pathway in major phenotypic manifestations of the hAPP AD model, on one hand through a careful lipidomics analysis, on the other hand through an elegant rescue of neurobehavioral phenotypes after a genetic manipulation of GIVA-PLA2 in the hAPP mice.We thank the reviewer for highlighting these strengths of our study.

Overall, this is a well done and important study with important implications for the prevention and treatment of AD.We thank the reviewer for these positive comments.

Positive comments

Reviewer #1Major criticisms1. If Abeta quantification was carried as cited (ref.9. originally Johnson-Wood et al., 1997), GuHCl was used for extraction. It is possible that efficacy of extraction may differ between wild-type Abeta and Arctic Abeta (Fig. 1. c-e). It is therefore necessary to confirm that the GuHCl-insoluble fractions do not contain any residual Abeta.To address this question, we dissolved Guaindine hydrochloride (GuHCl)-insoluble fractions with 80% formic acid followed by acid-urea gel/western blot analysis 1. In all three hAPP lines with or without Arctic mutation, no A was detected in the GuHCl-insoluble fractions from 2-4-weeks-old mice (this data was included into revised manuscript in Fig1f, lane 8-10). This result suggests that no detectable residual A in the GuHCl-insoluble fraction before plaque formation.

Additional experiments added

2. Is there any tauopathy or neurodegeneration in the aged ARC6 or ARC48 in EC or other cortical areas?We are currently studying the neurodegeneration and other pathological changes in these new ARC mouse models. More details will be reported in the sequential paper to further elucidate the role of amyloid plaque formation in Alzheimer’s disease.

For experiments take years to finish

Detailed characterization of pathological, behavioral and neuronalabnormalities in these mice prior to and after amyloid plaques are formed,similar to those performed by this group on earlier AD mouse models (Hsia et

Most of the important characterization experiments suggested by reviewer are in progress, but beyond the scope of this brief communication. Those characterizations will be reported in the sequential paper to elucidate the role of amyloid plaque formation in Alzheimer’s disease.However, we want to communicate with people in the field regarding some of the noteworthy evidences of Arctic mutant APP and Ab.

For experiments take years to finish

The authors do not comment on the study that injecting polyglutamine aggregates into the nucleus was toxic to mammalian cells (Yang et al., Hum Mol Genet 11:2905-2917, 2002). Also, how do the authors reconcile their observations that administration of Congo Red or trehalose, which inhibit the generation of aggregates are neuroprotective in vivo (Sanches et al., Nature 421:373-379, 2003; Tanaka et al., Nat Med 10:148-154, 2004). Studies in Drosophila also suggested that aggregation inhibitors showed efficacy (Apostol et al., PNAS 100:5950-5955,2003).We are grateful to the Referee for raising these points. Several studies have shown that some small molecules that interfere with aggregation improve symptoms and survival in mouse and fly models of HD2-4. Confusion has arisen because other studies identified manipulations that seemingly cause IBs to disappear but worsen the phenotype1,5-7. Our observations could reconcile these apparently contradictory results.

More explanations

However, for such a study, we need to know what proportion of the cells losing mRFP fluorescence by other techniques are dead by other criteria (e.g. nuclear fragmentation/ annexin V) and vice versa. The data in the Neuron submission showing rescue of this phenotype with anti-apoptotic approaches does not address the issue properly.

Previously, we used conventional approaches, such as assays of nuclear fragmentation and terminal deoxynucleotidyl transferase-mediated end-labeling (TUNEL), to characterize our neuronal model of HD1. These methods, we discovered, have several limitations. First, …Second, … Third, ….. For these reasons, we sought an assay that would provide us with an unequivocal determination of cell death, would be free of user-bias, and would not depend on a window of detection or on the activation of a particular cell death pathway.However, to address the Referee’s specific concern that neurons with inclusion bodies and intact mRFP fluorescence might, nonetheless, have already initiated apoptosis or might even be dead, we performed additional experiments. ….. These results have been added to the supplementary section of the manuscript (Fig. S5).

More explanations

If a "stupid" reviewer misunderstood your paper

•Truth hurts sometimes, but listen anyway.

•The typical reviewer spends two hours or less on your paper.

•Reviewer usually is an expert in the field. Why such an expert has trouble understanding your paper.

•This "stupid" reviewer will not disappear until you correct it.

•There must be something valuable in those reports. Salvage and incorporate them into your paper.

Do not attack reviewers

• Generally, it is not a good idea to berate the reviewers in the rebuttal letter.

• BAD: "The referee's idea is bad, but mine is good."

• GOOD: “The referee has an interesting notion, but the proposed idea is also good, particularly in light of XX or YY fact.

I have not found writing one bit easier today than it was 30 years ago. I still have to work at it very hard and make many revisions

Morton Grossman (>400 scientific papers, 134 editorials, 71 books

or book chapters)

Good luck, and happy publishing.

How to make a good power point slides for seminar

http://tw.youtube.com/watch?v=aFSTri0FhVA

Why good presentation really matters

If your audience can’t understand your talk, they may feel:

1. “I am too stupid to understand this speaker”

2. “This speaker is too stupid to make his/her presentation understandable.”

3. Zzzzzzz……

KISS – Keep It Simple Stupid

• Make the majority of the audience understand your talk• You should know

– What is the story you want to tell?– Who is the audience?– What data are required to tell the story and to sell your product?

• Goal– Send a clear message– Tell a clear story

Telling a story

• Formula– Beginning: Tell them what you’re going to tell them– Middle: Tell them– End: Tell them what you told them

Beginning

• Tell them what you’re going to tell them• Start SLOWLY

– Speak slowly– Short sentence– 1 point per sentence

• Set the stage (start with things that are known)

Why state the message at the beginning

• What about suspense?

• One goal → to get message across– Audience still awake– Stating early lets you repeat– Easier to follow the talk

Middle: Tell them

• Find a clear story line

• Make outline

• Build up a model

Experiments

• Question – why• Experiment – what you did• Result – what you found• Answer – what it means

End – told them what you told them

• Audience is tired. Make it easy for them• Restate the message• Fit the message into a broader context

– Application, future direction

• Exit line– Thank you, acknowledgment

Type of slides

• Model slide - Working model or summary

• Roadmap slide – outline and transition• Method slide• Transition slide

Fonts

• Use universal fonts (available for PC and Mac).• Commonly used fonts: Arial or Helvetica.

– When use Courier new or Times new roman, make them bold

– Comic looks cute but not good for formal talk

• Size – title: 30-36 points; text: 20-28 points• The bigger the audience/room is, the larger the font

should be used.• No mix fonts.• Use italics, bold, or color for emphasis

Slide title

• Every slide should have a title– Description of the data – Interpretative statement of the results

• Key point of the slide• Max three lines; better one line

General recommendations for text

• No more than 8-12 lines of text; ~ 8-10 words/line.• Use short phrases to state key points.• Use color to focus attention on key points.• Use space appropriately.

Keep the text simple

DATA

R6/2 mice

Andrews Andrews et al. Brainet al. Brain 1999;122:2353-63 1999;122:2353-63

HD gene-positive patients

D2

PET

CTL HD

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0.25

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nd(p

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Age (Weeks)

Striatum

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***p < 0.0001

***

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PPED2

PSSNR1

0

10

20

30

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NII+Cortex

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111/111

Graphics

• Keep them simple• Don’t directly copy from your paper• Large enough to see (for every details)

– Size of the room– Size of audience

• Sloppy slides suggest sloppy lab procedure

© J. Paul Robinson, Purdue University66 of 46

Data Slides

Here is something important…..

Make sure the color contrast is high

Label every line on the gel

Make sure your data stand up

Make sure your data stand up


Mean

EB

Flu

ore

scen

ce

0

4

8

12

HBSSTNF

HBSS L-arg L-argTNF

L-NMMA L-NMMATNF

a

aa

a

b

c

dd

Make graph clear and simple

NO modulators increase superoxide, TNK reduces O2-

Bars represent 1 SD mean

a,b,c,drepresentstatistical significancelevels


Mean

EB

Flu

ore

scen

ce

0

4

8

12

HBSSTNF

HBSS L-arg L-argTNF

L-NMMA L-NMMATNF

a

aa

a

b

c

dd

Keep the colors consistent through out the talk





Mean

EB

Flu

ore

scen

ce

0

4

8

12

HBSSTNF

HBSS L-arg L-argTNF

L-NMMA L-NMMATNF

a

aa

a

b

c

dd

Be careful when you use enhancement features




Backgrounds

• Be careful when using backgrounds available from templates

• A more conservative approach is safer• You want the audience to focus on your data, not your

background• If you must, use a simple color


Imaging, Flow Cytometry, and Functional Cytomics:

Applications of current cell analysis techniques

J. Paul Robinson, PhD

Purdue University Cytometry Laboratories

J. Paul Robinson, Ph.D., & Bartek Rajwa, Ph.D.

Purdue University Cytometry Laboratories

Imaging, Flow Cytometry, and Functional Cytomics Applications of current cell analysis techniques


What Resources are Required?

• Start with educational objectives and goals• Define needs based only on the educational

objectives• Initially identify minimal hardware requirements,

beg or borrow if necessary• Integrate staff into lab with scientific staff to

increase participation

78


Start with educational objectives and goalsDefine needs based only on the educational objectivesInitially identify minimal hardware requirements, beg or borrow if necessaryIntegrate staff into lab with scientific staff to increase participation

79


Start with educational objectives and goals Define needs based only on the educational

objectives Initially identify minimal hardware

requirements, beg or borrow if necessary Integrate staff into lab with scientific staff to

increase participation

8080

What Resources are What Resources are Required?Required?• Start with educational objectives and Start with educational objectives and

goalsgoals

• Define needs based only on the Define needs based only on the educational objectiveseducational objectives

• Initially identify minimal hardware Initially identify minimal hardware requirements, beg or borrow if necessaryrequirements, beg or borrow if necessary

• Integrate staff into lab with scientific staff Integrate staff into lab with scientific staff to increase participationto increase participation

81

What Resources are Required?• Start with educational objectives and

goals• Define needs based only on the

educational objectives• Initially identify minimal hardware

requirements, beg or borrow if necessary

• Integrate staff into lab with scientific staff to increase participation

82

Rat neutrophil oxidative burstwith nitric oxide modulators


0

4

8

12

HBSSTNF

HBSS L-arg L-argTNF

L-NMMA L-NMMATNF

a

a

a

b

c

d

Mea

n E

B F

luor

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nce

CondenserLens

Pinhole 1 Pinhole 2

ObjectiveLens

Specimen

Detector


Use of Color

• Color shows emphasis….BUT..• It should be used sparingly• Certain colors cannot be used together

– For example:– Red text cannot be used on blue backgrounds or vice versa– Blue text cannot be used on red backgrounds or vice versa

• Colors that should virtually never be used are:– Purple, pink and bright green

• Yellow can be used on black but never on white background


The computer vs. projector screen

• Colors that look great on your computer screen may be HORRIBLE on the projector screen.

• For example BLUE background CANNOT have black text.

Your computer SCREEN looks likethis….It’s just OK.

But this is what happens when it isprojected onto the screen….

Black Text looks fine on yourComputer screen Black Text looks bad after projection

Yellow is safer on blue background Yellow is safer on blue background


Advantages

Standard Assay• Uses whole blood• Cheaper than

microdrop

Gel Microdrop• Rare populations• Short incubation• Sort and recover live

cells

Source: One Cell System, 2002; BD Resource Manual, 2001

86

Advantages

Standard Assay Uses whole blood Cheaper than

microdrop

Gel Microdrop Rare populations Short incubation Sort and recover live

cells


87

AdvantagesStandard Assay

Uses whole blood Cheaper than

microdrop

Gel Microdrop Rare populations Short incubation Sort and recover live

cells



Animation

• How much animation is right?• Make sure you test it carefully!• A small amount of animation is good• Too much is “ditzy” and often annoys your audience

89 of 48

And for Imaging Technologies?

• DNA arrays

• “Quantitative” fluorescence assays

• High Throughput assays (96-384 well plates)

• Elispot

• Drug effect assays

•Toxicology assays

90 of 48

And for Imaging Technologies?

• DNA arrays

• “Quantitative” fluorescence assays

• High Throughput assays (96-384 well plates)

• Elispot

• Drug effect assays

•Toxicology assays


Hydrodynamically focused fluidics

•Increase pressure:•Widen core•Increase turbulence

Signal


Use diagrams or flow charts if possible

First Reactant Intermediate Last Reactant

Reagent A

Reagent B

Reagent C

Blocker 1

Note the stars indicating the number of mouse clicks left…

How many slides?

• Rule of thumb: Use 1 slide per minute of your allotted time including your opening and closing slides.

• 10 min talk: 9-11 slides



• Don’t race through slides

How to Talk

• Not a conversation, but an oration• Talk SLOWLY!

– Audience hearing it for the first time– Audience reading your slides– Non-native English speakers– If you talk quickly, people assume you’re nervous, and

they become nervous. – If you talk slowly, with pauses, people assume you’re

brilliant.

Your personal habits

• Standing: Face your audience. If you are very nervous, look only at people in the middle or back rows, or try to find a friendly face.

• Speech: Speak slowly, clearly, & deliberately – don’t say “Ummm”…or “you know….”….between every sentence– Every time you feel it coming on, take a breath

• Fidgeting: If you tend to play with the toys (like keys) or put your hands in pockets – hold the lectern.

• Humor: Use very sparingly, it can be an ice-breaker but it is very hard to do – my suggestion is to avoid it

Laser Pointers

• Don’t wave that thing!– People find it visually irritating– Detracts from what you’re saying

• Point to the item in question• Turn pointer off after you’ve pointed out item of

interest

How to Improve

• Practice. – 9 hours for a 20 minute talk

• Practice again.– Don’t look like you’re seeing the slides for the first

time.

• Practice in front of friends.– Ask for honest feedback. No one will spontaneously

tell you you’ve given a terrible talk.

Answering Questions

1. Listen carefully. Do not interrupt the questioner.

2. Repeat the question for the audience

3. If you do not understand the question, ask for more guidance

e.g. “I am not sure I understand the question, could you elaborate.”

4. If you then do not know the answer, try this:

a. “I am not sure of the answer, but one possible reason might be”

b. “I’d be happy to get back to you with the answer to your question after I do some research on the issue”

c. “I don’t know the answer to your question at this stage!”

5. NEVER argue with questioners

“Perhaps we can talk about this after the seminar”

“There is no way to get experience except through

experience.”

Documents

Manuscript submissions and revisions. The professional editors The editors are usually PhD in this field (many of them have postdoc training in good labs)