Archive for the ‘journal club’ Category


  1. Gonzalez P, Uhlinger KR, Lowe CJ. The Adult Body Plan of Indirect Developing Hemichordates Develops by Adding a Hox-Patterned Trunk to an Anterior Larval Territory. Curr Biol. 2016 Dec 7. pii: S0960-9822(16)31273-8. doi: 10.1016/j.cub.2016.10.047. [Epub ahead of print] PubMed PMID: 27939313.
    • Hejnol A, Vellutini BC. Larval Evolution: I’ll Tail You Later…. Curr Biol. 2017 Jan 9;27(1):R21-R24. doi: 10.1016/j.cub.2016.10.057. PubMed PMID: 28073016.


  1. Tornini VA, Puliafito A, Slota LA, Thompson JD, Nachtrab G, Kaushik AL, Kapsimali M, Primo L, Di Talia S, Poss KD. Live Monitoring of Blastemal Cell Contributions during Appendage Regeneration. Curr Biol. 2016 Nov 21;26(22):2981-2991. doi: 10.1016/j.cub.2016.08.072. PubMed PMID: 27839971; PubMed Central PMCID: PMC5121098.
  2. Currie JD, Kawaguchi A, Traspas RM, Schuez M, Chara O, Tanaka EM. Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools. Dev Cell. 2016 Nov 21;39(4):411-423. doi: 10.1016/j.devcel.2016.10.013. PubMed PMID: 27840105; PubMed Central PMCID: PMC5127896.
    • Weidinger G. Regeneration: Recorded Live! Curr Biol. 2017 Jan 9;27(1):R30-R33. doi: 10.1016/j.cub.2016.11.022. PubMed PMID: 28073020.


  1. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013 Oct 21;14(10):R115. [Epub ahead of print] PubMed PMID: 24138928.
  2. News: FDA Tells Google-Backed 23andMe to Halt DNA Test Service


  1. Kolb AW, Ané C, Brandt CR. Using HSV-1 Genome Phylogenetics to Track Past Human Migrations. PLoS One. 2013 Oct 16;8(10):e76267. doi: 10.1371/journal.pone.0076267. PubMed PMID: 24146849; PubMed Central PMCID:PMC3797750.
  1. Clark C, Austen O, Poparic I, Guthrie S. a2-Chimaerin Regulates a Key Axon Guidance Transition during Development of the Oculomotor Projection. J Neurosci.  2013 Oct 16;33(42):16540-51. doi: 10.1523/JNEUROSCI.1869-13.2013. PubMed PMID:24133258.
  2. Lange M, Neuzeret F, Fabreges B, Froc C, Bedu S, Bally-Cuif L, Norton WH. Inter-individual and inter-strain variations in zebrafish locomotor ontogeny. PLoS One. 2013;8(8):e70172. doi: 10.1371/journal.pone.0070172. eCollection 2013.  PubMed PMID: 23950910; PubMed Central PMCID: PMC3739779.


  1. News: Two famously ‘cured’ Boston HIV sufferers are found to STILL have the virus ‘hiding’ in their blood 


Stem cells

  1. Abad M, Mosteiro L, Pantoja C, Cañamero M, Rayon T, Ors I, Graña O, Megías D, Domínguez O, Martínez D, Manzanares M, Ortega S, Serrano M. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature. 2013 Sep 11. doi: 10.1038/nature12586. [Epub ahead of print] PubMed PMID: 24025773.
    • Commentary: De Los Angeles A, Daley GQ. Stem cells: Reprogramming in situ. Nature. 2013 Sep 11. doi: 10.1038/nature12559. [Epub ahead of print] PubMed PMID: 24025771.
    • News coverage: More-Primitive Stem Cells Produced

Ig Nobel price 2013


  1. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, Bean T, Barclay W, Deeks JJ, Lalvani A. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013 Sep 22. doi: 10.1038/nm.3350. [Epub ahead of print] PubMed PMID: 24056771.


  1. Lee MT, Bonneau AR, Takacs CM, Bazzini AA, Divito KR, Fleming ES, Giraldez AJ. Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Nature. 2013 Sep 22. doi: 10.1038/nature12632. [Epub ahead of print] PubMed PMID: 24056933.



  1. Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, Scott DA, Inoue A, Matoba S, Zhang Y, Zhang F. Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity. Cell. 2013 Sep 12;154(6):1380-9. doi: 10.1016/j.cell.2013.08.021. Epub 2013 Aug 29. PubMed PMID: 23992846.
  2. Yang H, Wang H, Shivalila CS, Cheng AW, Shi L, Jaenisch R. One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering. Cell. 2013 Sep 12;154(6):1370-9. doi: 10.1016/j.cell.2013.08.022. Epub 2013 Aug 29. PubMed PMID: 23992847.
  3. Mali P, Aach J, Stranges PB, Esvelt KM, Moosburner M, Kosuri S, Yang L, Church GM. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol. 2013 Sep;31(9):833-8. doi: 10.1038/nbt.2675. Epub 2013 Aug 1. PubMed PMID: 23907171.
  4. DiCarlo JE, Norville JE, Mali P, Rios X, Aach J, Church GM. Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems. Nucleic Acids Res. 2013 Apr;41(7):4336-43. doi: 10.1093/nar/gkt135. Epub 2013 Mar 4. PubMed PMID: 23460208; PubMed Central PMCID: PMC3627607.

Stem cells

  1. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013 Aug 9;341(6146):651-4. doi: 10.1126/science.1239278. Epub 2013 Jul 18. PubMed PMID: 23868920.


  1. Shomrat T, Levin M. An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration. J Exp Biol. 2013 Jul 2. [Epub ahead of print] PubMed PMID: 23821717.
  2. Esposti F, Johnston J, Rosa JM, Leung KM, Lagnado L. Olfactory Stimulation Selectively Modulates the OFF Pathway in the Retina of Zebrafish. Neuron. 2013 Jul 10;79(1):97-110. doi: 10.1016/j.neuron.2013.05.001. PubMed PMID: 23849198.
    • Commentary: “Dowling JE. Olfaction and Vision Meet in the Retina. Neuron. 2013 Jul 10;79(1):1-3. doi: 10.1016/j.neuron.2013.06.024. PubMed PMID: 23849191.


  1. Endeman D, Klaassen LJ, Kamermans M. Action spectra of zebrafish cone photoreceptors. PLoS One. 2013 Jul 5;8(7):e68540. doi: 10.1371/journal.pone.0068540. Print 2013. PubMed PMID: 23861916; PubMed Central PMCID: PMC3702584.


  1. Poznik GD, Henn BM, Yee MC, Sliwerska E, Euskirchen GM, Lin AA, Snyder M, Quintana-Murci L, Kidd JM, Underhill PA, Bustamante CD. Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science. 2013 Aug 2;341(6145):562-5. doi: 10.1126/science.1237619. PubMed PMID: 23908239.
  2. Francalacci P, Morelli L, Angius A, Berutti R, Reinier F, Atzeni R, Pilu R, Busonero F, Maschio A, Zara I, Sanna D, Useli A, Urru MF, Marcelli M, Cusano R, Oppo M, Zoledziewska M, Pitzalis M, Deidda F, Porcu E, Poddie F, Kang HM, Lyons R, Tarrier B, Gresham JB, Li B, Tofanelli S, Alonso S, Dei M, Lai S, Mulas A, Whalen MB, Uzzau S, Jones C, Schlessinger D, Abecasis GR, Sanna S, Sidore C, Cucca F. Low-pass DNA sequencing of 1200 Sardinians reconstructs European Y-chromosome phylogeny. Science. 2013 Aug 2;341(6145):565-9. doi: 10.1126/science.1237947. PubMed PMID: 23908240.
  3. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol. 2013 Jun 23. doi: 10.1038/nbt.2623. [Epub ahead of print] PubMed PMID: 23792628.

These days many cherish “hypothesis-driven” research and trash everything that is observational, exploratory and non-translational. And yet the hypothesis in many research is “post-research” hypothesis. The “hypothesis” itself is also often generated for the sake of having an hypothesis; the essence of the research can still be exploratory.

So when funding is getting scarce and the pressure of coming up with beautiful hypothesis is mounting, one must ask what the value of hypothesis-driven research is. Is it the only way to get important findings? Is it delivering more than other “inferior” approaches?

As I am thinking about these questions and situation all the time, I am leading a journal club in the lab on 8/1 and trying to discuss the philosophical aspects of this with my lab members. And I want to write this down and have a record before we do so. We will read a few articles:

  1. Pisani E. Has the internet changed science? Prospect 2010; 177:54 [pdf]
  2. Kell DB, Oliver SG. Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. Bioessays. 2004 Jan;26(1):99-105. PubMed PMID: 14696046.
  3. Ioannidis JP. Why most published research findings are false. PLoS Med. 2005 Aug;2(8):e124. Epub 2005 Aug 30. PubMed PMID: 16060722; PubMed Central PMCID: PMC1182327.

and discuss a few questions, in addition to the ones I have above:

  1. Are data mining or descriptive research useless?
  2. What are the downsides of doing “hypothesis-driven research”?
  3. Are we/funding agencies/authorities doing the society a favor by insisting scientists to have a hypothesis/justification attached to a research idea? how about research that has translational value (i.e. curing disease)? or technical value (e.g. developing a cheaper and faster way to sequence human genome?)
  4. Is/Can there a balance between different scientific research approaches?


  1. Shive HR, West RR, Embree LJ, Azuma M, Sood R, Liu P, Hickstein DD. brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19350-5. Epub 2010 Oct 25. PubMed PMID: 20974951.
  2. Jain S, Heutink P. From single genes to gene networks: high-throughput-high-content screening for neurological disease. Neuron. 2010 Oct 21;68(2):207-17. Review. PubMed PMID: 20955929.

Eye Disease

  1. Linder B, Dill H, Hirmer A, Brocher J, Lee GP, Mathavan S, Bolz HJ, Winkler C, Laggerbauer B, Fischer U. Systemic splicing factor deficiency causes tissue-specific defects: A zebrafish model for Retinitis pigmentosa. Hum Mol Genet. 2010 Nov 3. [Epub ahead of print] PubMed PMID: 21051334.


  1. Lek M, Dias JM, Marklund U, Uhde CW, Kurdija S, Lei Q, Sussel L, Rubenstein JL, Matise MP, Arnold HH, Jessell TM, Ericson J. A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral neural patterning. Development. 2010 Dec;137(23):4051-60. PubMed PMID: 21062862.
  2. Green AA, Kennaway JR, Hanna AI, Bangham JA, Coen E. Genetic Control of Organ Shape and Tissue Polarity. PLoS Biol. 2010 Nov 9;8(11):e1000537. PubMed PMID: 21085690.
  3. Cui ML, Copsey L, Green AA, Bangham JA, Coen E. Quantitative Control of Organ Shape by Combinatorial Gene Activity. PLoS Biol. 2010 Nov 9;8(11):e1000538. PubMed PMID: 21085695.

Eye Development

  1. Billings NA, Emerson MM, Cepko CL. Analysis of Thyroid Response Element Activity during Retinal Development. PLoS One. 2010 Oct 29;5(10):e13739. PubMed PMID: 21060789; PubMed Central PMCID: PMC2966421.
  2. Phillips MJ, Otteson DC. Differential expression of neuronal genes in Muller glia in two- and three-dimensional cultures. Invest Ophthalmol Vis Sci. 2010 Nov 4. [Epub ahead of print] PubMed PMID: 21051699.

Stem Cells

  1. Hanna JH, Saha K, Jaenisch R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell. 2010 Nov 12;143(4):508-25. PubMed PMID: 21074044.
  2. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR. A model for neural development and treatment of rett syndrome using humaninduced pluripotent stem cells. Cell. 2010 Nov 12;143(4):527-39. PubMed PMID: 21074045.


  1. Newman M, Lardelli M. A hyperactive sleeping beauty transposase enhances transgenesis in zebrafish embryos. BMC Res Notes. 2010 Nov 4;3(1):282. [Epub ahead of print] PubMed PMID: 21050486.


  1. Wyart M, Botstein D, Wingreen NS. Evaluating Gene Expression Dynamics Using Pairwise RNA FISH Data. PLoS Comput Biol. 2010 Nov 4;6(11):e1000979. PubMed PMID: 21079668; PubMed Central PMCID: PMC2973809.

Systems Biology

  1. Lehner B. Conflict between Noise and Plasticity in Yeast. PLoS Genet. 2010 Nov 4;6(11):e1001185. PubMed PMID: 21079670; PubMed Central PMCID: PMC2973811.
  2. Li J, Yuan Z, Zhang Z. The cellular robustness by genetic redundancy in budding yeast. PLoS Genet. 2010 Nov 4;6(11):e1001187. PubMed PMID: 21079672; PubMed Central PMCID: PMC2973813.

Ethics, Society and Legal Issues

  1. Johnson DG. The role of ethics in science and engineering. Trends Biotechnol. 2010 Sep 9. [Epub ahead of print] PubMed PMID: 20832883.

I suggest we read a paper recently published in Science. The title is “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa”. Retinal pigmentosa is so far found to be caused by diverse mutations in 44 genes. Patients with this diease will irreversibly lose their vision, as rod photoreceptors will die early and cone photoreceptor will be light-insensitive owing to the morphological change. But normally cone photoreceptors could persist longer. In this study, the authers genetically targeted a light activated chloride pump, which is one of the candidates for reactivating vertebrate photoreceptors, into the photorecepors of mouse models of retinitis pigmentosa by means of adneo-associated viruses, and successfully restored their light sensitivity. They also found the protein could reactivate the light-insensitive human photoreceptors in ex vivo retinas. Is this a good news for people who suffer from retinitis pigmentosa and blindness? Let’s find out together.

Link to the paper:

We will all read two short articles about Cystic Fibrosis:

  • Couzin-Frankel J. The promise of a cure: 20 years and counting. Science. 2009 Jun 19;324(5934):1504-7.
  • Pearson H. One gene, twenty years. Nature. 2009 Jul 9;460(7252):164-9.

Each one of us will then pick one of the following topics, elaborate the discussion by reading an additional latest reference of your choice and present the major ideas in the lab meeting.  (Liyun, as a physician for years, should pick up a more research-based topic).

The format will be a 10-min presentation followed by 5-min discussion. If you are discussing a research paper, the breakdown should be as follows: 5-min for background+experimental design, 5-min for 1-2 major findings. For a review paper, the breakdown should be approximately 3 mins for each major idea. The presentation should have no more than 4 slides, preferably 3, you can also use the board. We will also bring a timer.

I suggest the following six topics:

  1. Pathophysiology
  2. Etiology and epidemiology
  3. General therapeutic approaches excluding gene therapy
  4. Functional characterization of CFTR
  5. Animal models, challenges and prospects
  6. Gene therapy, challenges and prospects

Please reply and this thread to select your topic, and upload both your presentation and the reference article to the appropriate lab meeting folder.  I look forward to discussing these ideas with you!