Here are the research highlights from the current issue of Development:

Laminin cue for epithelial polarity

During the development of many animal organs, mesenchymal cells co-ordinately polarize to form epithelial sheets or tubes. In vitro studies have suggested that the extracellular matrix component laminin functions as a polarity cue during this mesenchymal to epithelial transition. Here (p. 2050), Jeffrey Rasmussen and colleagues provide in vivo evidence for laminin’s involvement in polarization by studying the development of the C. elegans pharynx, an epithelial tube that forms from pharyngeal precursor cells (PPCs). The researchers show that cell fate regulators, including the transcription factor PHA-4, cause the PPCs to form a bilaterally symmetric, rectangular array of cells called the ‘double plate’. PPC polarization and apical PAR localisation begin in the double plate cells, which then undergo apical constriction to form a cylindrical cyst. Notably, laminin provides an essential cue that orients the apical localisation of the PAR-3 complex in the double plate but not in the developing C. elegans intestine. Thus, the researchers conclude, laminin is an early polarizing cue for some but not all epithelia.

Why oocytes are predisposed to aneuploidy

During mitosis, the spindle assembly checkpoint (SAC) coordinates proper bipolar chromosome attachment with the anaphase-promoting complex/cyclosome (APC/C)-mediated destruction of cyclin B1 that is required for anaphase onset, thereby avoiding chromosome mis-segregation and aneuploidy. The generation of a Mad2-based signal at kinetochores is central to current models of SAC-based APC/C inhibition: during mitosis, the kinetochores of polar chromosomes (non-aligned bivalents), which are at the greatest risk of mis-segregating, preferentially recruit Mad2, which couples SAC activation to aneuploidy risk. Paradoxically, although an SAC operates in mammalian oocytes, meiosis I is notoriously error prone. Two papers in this issue investigate this long-standing puzzle.

On p. 1947, Keith Jones and colleagues examine the timing of Mad2 loss from mouse oocyte kinetochores. The formation of stable kinetochore-microtubule attachments in mid-prometaphase (3-4 hours before anaphase), they report, coincides with the loss of Mad2 from the kinetochores and the start of APC/C-mediated cyclin B1 destruction. Thus, SAC inhibition of the APC/C ends in mid-prometaphase. However, in a third of oocytes examined, this timing did not coincide with bivalent congression. Notably, the presence of non-aligned bivalents (which were weakly positive for Mad2, under less tension than congressed bivalents, and in the process of establishing correct bi-orientation) did not affect the time between APC/C activation and anaphase onset, and non-aligned bivalents sometimes persisted until anaphase, resulting in homologue non-disjunction. Thus, in oocytes, a few erroneous microtubule-kinetochore attachments may go uncorrected because they do not generate a sufficient SAC ‘wait anaphase’ signal to inhibit the APC/C.

On p. 1941, Liming Gui and Hayden Homer investigate how the SAC responds to polar chromosomes during meiosis I in oocytes. They show that Mad2 is not preferentially recruited to the kinetochores of the rare polar chromosomes that occur in wild-type mouse oocytes or to the kinetochores of the more abundant polar chromosomes that are found in oocytes depleted of the kinesin-7 motor CENP-E. Moreover, in CENP-E-depleted oocytes all the kinetochores eventually become devoid of Mad2, even though the capacity of the chromosomes to form stable attachments to the spindle is severely compromised. These and other findings suggest that SAC signalling is uncoupled from chromosomal position during meiosis I in mouse oocytes, thereby predisposing oocytes to aneuploidy.

Digging out the flowery function of APETALA2

The regulation of gene expression by transcription factors drives cell fate specification during development. In Arabidopsis, transcription factors encoded by four classes of homeotic genes control floral organ identity. The A-class gene APETALA2 (AP2) promotes sepal and petal identity and restricts expression of the C-class gene AGAMOUS (AG), which specifies stamen and carpel identity, but how does AP2 perform these functions? On p. 1978, Xuemei Chen and co-workers report that AP2 recognises and acts through an AT-rich sequence element. The researchers show that AP2R2 (one of two DNA-binding domains in AP2) binds a non-canonical AT-rich target sequence in vitro and that the presence of this sequence in the second intron of AG is important for the restriction of AG expression in vivo. Other experiments indicate that AP2 directly regulates AG expression in young flowers through this sequence element, which is highly conserved in Brassicaceae. Together, these findings shed light on the molecular mechanism underlying AP2 action and provide a missing link in the mechanisms controlling flower development.

Membrane trafficking and epithelial polarity

Biological tubes composed of polarized epithelial cells perform many functions in multicellular organisms. The establishment and maintenance of epithelial polarity depend on polarized trafficking of membrane components to the apical or basolateral domains of epithelial cells, but exactly how trafficking regulates epithelial polarity is unclear. In this issue, two papers describe a new and unexpected role for the post-Golgi vesicle coat clathrin and its adaptor AP-1 in apical sorting and lumen formation in the C. elegans intestine.

On p. 2061, Grégoire Michaux and colleagues report that the clathrin adaptor AP-1 is required for epithelial polarity in the C. elegans intestine. Depletion of AP-1 subunits does not affect the establishment of epithelial polarity or the formation of the intestinal lumen, the researchers report. However, they show that AP-1 is essential for the apical localisation of the oligopeptide transporter PEPT-1 and the polarity proteins PAR-6 and CDC-42, and for the basolateral distribution of the monocarboxylate transporter SLCF-1. They also show that AP-1 depletion triggers the formation of ectopic apical lumens between intestinal cells along the lateral membranes later during embryogenesis.

On p. 2071, Verena Gobel and colleagues perform an unbiased RNAi screen for apicobasal polarity and tubulogenesis defects in the C. elegans intestine and identify clathrin and AP-1 as being required for apical polarity and lumen formation. The researchers show that clathrin/AP-1-mediated polarized transport co-operates with a sphingolipid-dependent apical sorting process. Furthermore, they report, the depletion of clathrin, AP-1 or glycosphingolipid biosynthetic enzymes causes a set of apical membrane proteins (including PAR-6) to mislocalise basolaterally and generate ectopic lateral lumens. Finally, they show that clathrin-coated and sphingolipid-rich vesicles assemble at polarized plasma membrane domains in a co-dependent and AP-1-dependent manner.

Together, these findings suggest that clathrin/AP-1 controls both basolateral and apical sorting, an unexpected finding given that, until now, clathrin and its AP-1 adaptor had been thought to regulate only basolateral sorting in mammalian epithelia. Importantly, these findings indicate that this newly discovered clathrin/AP-1 function in apical sorting is required to regulate epithelial polarity in vivo in a tubular epithelium and that the clathrin/AP-1 apical sorting pathway converges with a sphingolipid-dependent apical trafficking path.

Plus…

Tet family proteins and 5-hydroxymethylcytosine in development and disease

Over the past few decades, DNA methylation at the 5-position of cytosine (5-methylcytosine, 5mC) has emerged as an important epigenetic modification that plays essential roles in development, aging and disease. In this Issue, Tan and Shi provide an overview of the role of Tet family proteins and 5hmC in development and cancer. See the Primer article on p. 1895

25 years of Development!

The Journal of Embryology and Experimental Morphology (JEEM) was founded in 1953, but it wasn’t until 1987, in a bold move by The Company of Biologists and the journal’s editors, that the journal was rebranded, restyled and relaunched as the journal we now know as Development.

We’ll be celebrating celebrating our quarter-century throughout the year, but to kick-start the celebrations we’ve invited past and present Editors in Chief of Development to share their memories and thoughts on their time in charge.

See the Editorials from Chris Wylie, Jim Smith and Olivier Pourquie.

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Postdoctoral Positions, St. Jude Children’s Research Hospital, Memphis, TN, USA

Postdoctoral Positions in Molecular and Developmental Biology are available to study the cellular and molecular mechanisms controlling vertebrate organogenesis. We are particularly interested in the development of the lymphatic vasculature and the visual system. We use available mouse models to understand the mechanisms regulating these processes in normal and pathological conditions.

Highly motivated individuals who recently obtained a PhD. or MD degree and have a strong background in molecular and developmental biology are encouraged to apply. Interested individuals should send their curriculum vitae, a brief description of their research interests, and the names of three references to:

Guillermo Oliver, Ph.D
guillermo.oliver@stjude.org
Department of Genetics
St. Jude Children’s Research Hospital
332 N. Lauderdale
Memphis, TN 38105 USA
www.stjude.org/departments/oliver.htm

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Abstract & Bursary deadline: 11 May | Registration deadline: 31 May

Now in its third year, this Wellcome Trust meeting will focus on the biology of sub-nuclear structures including the nucleolus, cajal and PML bodies. These structures have key roles in normal and diseased cells and they interact in a dynamic way. A fundamental understanding of these sub-nuclear structures can lead to advances in our understanding of infectious disease and cancer.

The conference will bring together cell biologists, microbiologists and virologists working on normal and tumor cells and researchers interested in how these structures are affected by infectious and acquired disease across all eukaryotic systems.

Scientific Organisers:
Susan Baserga Yale University, USA
Julian Hiscox University of Leeds, UK

David Matthews University of Bristol, UK
Brian McStay NUI Galway, Ireland

Invited Speakers include:
Susan Baserga Yale University, USA
Richard Gardner University of Washington, USA
Ingrid Grummt Deutsches Krebsforschungszentrum, Germany
Ross Hannan Peter MacCallum Cancer Centre, Australia
Valerie Lallemand-Breitenbach Hopital Saint-Louis, France
Angus Lamond University of Dundee, UK
Greg Matera University of North Carolina, USA
Brian McStay NUIG, Ireland
Karla Neugebauer Max Planck Institute, Germany
Craig S. Pikaard Indiana University, USA
Michael Taliansky The James Hutton Institute, UK
David Tollervey University of Edinburgh, UK
Adrian Whitehouse University of Leeds, UK

Abstract submission is strongly encouraged as several talks will be selected from abstracts.

For more information: https://registration.hinxton.wellcome.ac.uk/display_info.asp?id=294

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One of the covers of Development this year is reserved for an image from the International Course on Developmental Biology, UNAB, Quintay-Chile. This course ran from 5-17 January in Chile. You can read a report from the course on the Node.

Which image will get the coveted cover spot is up to you to decide. Choose your favourite before May 21st, noon GMT. There are 8 images to choose from. Click any of them to see a bigger version.

1. Six zebrafish

2. Drosophila ovaries, HisGFP

3. Planarian in situ

4. Planarian confocal

5. Sea urchin

6. Drosophila embryo, Knirps

7. Chick embryo

8. Xenopus embryo, sox3

(3 votes)

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The winner of the first round of images from the 2011 Woods Hole Embryology Course is in. This beautiful image of a skate got almost half of the votes cast, and won by a large margin:

The image shows the ventral surface of the skate Raja prepared by alcian blue and alizarin red staining for cartilage and bone. (With additional staining of the ampullary canals surrounding the face.) It was taken by David Gold (University of California, Los Angeles), Lynn Kee (University of Michigan), and Meghan Morrissey (Duke University).

The skate will appear on the cover of Development in the next few weeks.

The runner-up mouse image was taken by Samantha Jones (Vassar), a course assistant in the 2011 Woods Hole Embryology Course, and both the snake and the chameleon images were taken by course students Jake Hines (University of Colorado – Denver) and Nate Peters (University of Washington).

Before we go on to round 2, we’ll first have a few images from another developmental biology course. They should be up on the Node tomorrow – stay tuned!

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Upcoming deadlines: oral abstracts – June 11, 2012

Topics:
• Genes, lipids and systemic inflammatione
• Early inflammatory and immune-driven atherogenesis
• Atheroprogression, ER-stress and unstable plaques
• Novel therapeutic options involving miRNAs

Speaker list:
Full speaker list available on meeting website.

Meeting website:
http://www.abcam.com/Munich

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Tuesday: Cell cycling and growth, stem cells and fate, and medal-winners’ lectures

Buzz Baum opened the cell cycle and growth in development session with a talk about his lab’s work at UCL on cell shape changes during mitosis in dissociated culture and in epithelial sheets. The talk covered cell rounding on entry into mitosis due to actin remodelling and the links between cell shape change and successful mitosis progression. Anna Philpott of the University of Cambridge discussed the regulation of proliferation and differentiation by post-translational modifications, including the accumulation of multi-site phosphorylation events, in neurogenesis.

Alison Lloyd gave a talk on Schwann cell dedifferentiation and proliferation in adult regeneration and the behaviour of proliferative Schwann cells after injury. She also discussed results from a novel mouse model of neurofibroma from her lab at the MRC Laboratory for Molecular Cell Biology and the UCL Cancer Institute. Fumio Matsuzaki of RIKEN CDB described asymmetric, symmetric and the rarely-observed oblique stem cell divisions in the subventricular zone, and their potential involvement in altering the balance of cortical progenitor numbers and promoting brain expansion in mammalian brain evolution.

The second poster session was held over Tuesday lunchtime, concurrent with a seminar on Huygens deconvolution in microscopy sponsored by Scientific Volume Imaging.

Stem cells and cell fate choice were the topics of the afternoon session. The many interesting presentations on stem cell topics in this and other sessions were an excellent reminder of the degree to which stem cell biology is integral to many developmental biology subfields. Sally Lowell’s talk on priming pluripotent cells for differentiation first established an incremental, rather than binary, model for progressive ES cell differentiation, before presenting findings on pro-differentiation signalling and transcription factor interactions. Mario Stavridis, a young PI at Dundee University, gave a fascinating talk on post-translational modification with beta-O-N-acetylated glucosamine, a parallel mechanism to protein phosphorylation that regulates embryonic stem cell differentiation. Berenika Plusa presented wonderful videos of live cell sorting in transgenic mouse blastocysts, showing cell type emergence and behaviour during the establishment of cell fate.

Josh Brickman spoke on lineage priming in embryonic stem cells, looking at the small initial differences in key molecule transcription and translation that prime stem cells to later adopt different fates. Soshei Yoshida from the National institute for Basic Biology, Japan, capped the session with a report on the process of spermatogenic stem cell self-renewal and progressive differentiation in the live mouse testis, discussing  how continuity in mouse spermatogenesis is promoted by the long-term maintenance of a range of undifferentiated progenitor cell types.

The Beddington medal was awarded to Boyan Bonev, who gave an excellent talk on his PhD work in Nancy Papalopulu’s lab on the role of microRNA-9 in neural progenitor development variation in space and time. Mutual regulation and oscillation between microRNA-9 and Hes transcription was found to produce a delayed trigger for neuronal differentiation.

The Waddington medal was presented to Alfonso Martinez-Arias of Cambridge University. As is traditional, his talk provided a retrospective of his life and career, with the inclusion of a number of special effects and musical numbers along with descriptions of his work on key Drosophila developmental pathways and cell fate determination. He closed his talk with words of solidarity for the upcoming generation of young scientists.

The evening graduate symposium was opened by Daphne Verleyen from the University of Leuven, who continued an emerging theme of the conference with her talk on left-right axis formation via cilia behaviour in Kupffer’s vesicle. She described results from a g-protein coupled receptor mutant zebrafish line with axis formation defects. Debbie McIntosh from the University of Dundee spoke on replication fork formation in stressed and cancerous cells, describing the results of a molecular screen on replication fork behaviour. Keliya Bai from the University of Aberdeen talked on epithelial elongation in c. elegans embryos through actin cytoskeleton contraction, and discussed an extensive screen carried out for components of the actin-anchoring complex.

Eight BSDB and BSCB poster prize winners were announced at the conference dinner, including Stephen Fleenor, Ricardo Laranjeiro, Tom Pettini and Jorge Beira. The delicious and social 3-course conference dinner was followed by disco music and dancing, over which a discrete veil will be drawn. A good time was had by all.

Wednesday: in vitro models of development and regeneration

The last session on in vitro models of developmental biology included talks from a number of regenerative medicine biologists, who provided a different perspective on in vitro culture as a tool for clinical applications as well as a model for examining tissue and cell function.

Keith Baar from UC Davis opened the day with his work on growing ligaments for transplant and using cultured ligaments as high throughput test bed for BMPs, FGFs and other combinations of molecules to examine their roles in tendon development. Andrea Vortkamp from University Duisberg-Essen presented results from analysis of chondrocyte development in a mouse mutant model of tricho-rhino-phalangeal syndrome, caused by Trps1 mutation, which is characterised by shortened limbs. The mutation appears to cause defects in cell cycle progression in chondrocytes due to effects on chromatin acetylation levels.

Masayuki Yamamoto from Tokyo Women’s Medical University gave an energetic talk on shyabu-shyabu bioengineering, which creates scaffold-free thin layers of tissue, including cornea, esophageal epithelium and skeletal muscle for human transplant. The culture technique used a polymer with temperature dependant cell-adhering properties, allowing cells and ECM to be harvested as a single sheet with the now-available UpCell dishes. Fiona Watt, head of the Centre for Stem Cell and Regenerative medicine at KCL, finished the conference on a high note with her talk on epidermal stem cell and niche interactions and responses of these groups of cells to microenvironmental cues. Her talk highlighted the research progress made through close collaboration with chemists and bioengineers in producing faithful and incisive in vitro models of the epithelial stem cell niche.

As always, the BSDB Spring meeting was a chance to see a good cross-section of current developmental biology research and – thanks to the BSCB joint meeting – catch up on relevant cell biology topics in the same place. It was also great to meet up with so many people from previous years’ conferences and see how their research has evolved. I look forward especially to seeing JSDB members again in future conferences.

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The 2012 Spring meeting of the British Society for Developmental Biology was held on the 15^th-18^th April at the spacious campus of Warwick University.  The meeting was held jointly with the Japanese Society for Developmental Biology and the British Society for Cell Biology. Many delegates from the JSDB attended, presented interesting talks and posters and greatly enlivened proceedings.

Sunday: Plenary lectures

The evening BSDB plenary lecture was given by Denis Duboule on the vertebrate Hox clock, describing the regulation of temporally and spatially collinearly expressed Hox genes. Focusing on the HoxD cluster, he described the use of ChIP and chromatin crosslinking to map the state of Hox gene packaging at different points in the Hox expression clock, presenting a directional chromatin transition-mediated model for temporal regulation of Hox gene expression within a Hox cluster. The BSCB plenary lecture by J.Richard McIntosh of the University of Colorado discussed microtubule tips as mechano-chemical devices, describing work showing how microtubules are capable of transporting loads at the depolymerising pole of the microtubule through the behaviour of depolarising filaments.

The joint plenary session was a great start to the conference on Sunday night, followed by the student and post-doc social pub quiz (joined by a few BSDB committee members), a great chance for some in-depth student socialising. Honourable mention to the winners of the coveted ‘best team name’ prize, Insane in the Phospholipid Bilayer, for making everyone laugh.

Monday: Systems biology, scientific careers,  imaging in development, and a turbulent AGM

The day’s first session on systems biology and next generation genome sequencing was opened by Duncan Odom speaking on transcriptional regulation in mammals, looking in particular at non-conserved promoter sequences that produce conserved  transcription factor binding patterns along the cis-regulatory region. Shane Herbert described the role of the homeobox gene hlx1 in sprouting endothelial tubules in zebrafish angiogenesis, introducing the tip/stalk model of growing blood vessels that appeared again in later talks. Erika Sasaki of the Institute for Experimental Animals in Kawasaki gave a fascinating talk on the use of lentiviral vectors in the generation of transgenic marmosets and the applications of transgenic primates in neurological and preclinical research. Kazuo Emoto from the Osaka Bioscience Institute opened the second half of the session with a talk on the shaping of Drosophila sensory neuron dendritic trees into sensory lattices through growth, calcium-current related pruning, regrowth and reshaping.

The Monday lunchtime career panel of PIs arranged by conference organiser Kim Dale dispensed advice and answered post-doc and student questions. The process of carving out a distinct and different niche in your field was discussed, as well as the importance of having and nurturing a passion for your chosen research subject – to sustain you through the inevitable lows (“It doesn’t stop hurting, but you eventually grow numb…”) of labwork, publishing and funding as well as the highs.  The impact of uncertainty and mobility in scientific careers on partners was also discussed, with the panel mentioning the necessity of discussing the burdens of scientific spouses. There was also mention of the importance of awareness of the ticking fellowship clock, with panellists stressing that many independent fellowships are restricted to applicants within 6 years of their PhD award.  For those interested in interdisciplinary research, the EIPOD EMBL postdoctoral fellowship program was recommended later in the conference.

The Monday afternoon session contained a range of talks on imaging space and time during development. Elliot Meyerowitz of the new Sainsbury Laboratory in Cambridge (who have a stated wealth of funding, positions and space, for all the plant developmental biologists reading) gave the lone but highly engaging plant development talk of the conference on shoot apical meristem patterning, including computer modelling of the role of both morphogens and physical forces on cells in the spiral pattern of meristem development. Toshiko Fujimori presented findings on cilia development and function in the mouse oviduct. He focused on the role of planar cell polarity in cilia orientation and oviduct membrane folding, demonstrating the links between micro and macroscopic organ morphology.

Antonio Jacinto’s talk on epithelial wound closure showcased some interesting videos of laser ablation and wound healing in Drosophila epithelial sheets, unpicking the rapid cytoskeletal processes behind the epithelial cell reshaping response to injury. Georgina Stooke-Vaughn from Sheffield University gave an assured talk on her ongoing PhD work on otolith development and hair cell cilia in the developing zebrafish vestibular system. Ryoichiro Kageyama of Kyoto University spoke on ultradian (shorter than circadian) rhythms in the somite segmentation clock in mouse, focusing on the processes behind and downstream of oscillations in Hes7 expression in the presomitic mesoderm. Hes expression oscillation was a popular theme, also appearing in several posters and the Beddington medal talk.

Finishing the afternoon session with a bang, the Hooke medal talk was delivered by Holger Gerhardt of Cancer Research UK on cell competition and vascular development in zebrafish, discussing tip and stalk cell dynamics in growing epithelial tubules. He presented both experimental and compelling visualised mathematical model evidence for a regulatory network involving VEGF and Notch that patterns angiogenic branching at intervals along the zebrafish spine.

The BSDB AGM took place on Monday evening. The vote to fill 3 open BSDB committee spaces was held, and it was announced later in the conference the new members are Anna Philpott, Jo Begbie and Henry Roehl. It was also announced that future spring meetings will be held at Warwick University for the next few years.

The evening poster session was lively and stimulating, with freely flowing ideas and beer.

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Discussions
We launched an essay competition, “Developments in development”. If you have any thoughts on the future of developmental biology – whether it’s about techniques, funding, or the general direction of the field – submit an essay before July 2nd, for a chance to be published in Development. For full details, see this post.

Speaking of the future, Tom Butts considered the recent “Academic Spring” movement. What is it, and is the name appropriate? Weigh in the comments of the post.

“Such as it is, the academic spring is not a movement directed at individual governments, but at international business practices – in that sense it shares more in common with the Occupy movement than the Arab Spring. It is not an undirected and unpredictable public protest movement, but a quiet and deliberate articulation of objection to a single company, in adherence to a well thought through and principled position. It is then, certainly academic. I’m just not sure it has sprung yet.”

Conferences

Conference season is in full swing. Have you been to any meetings yet? Vicky Hatch attended the 2012 UK National Xenopus Conference, and shared her experience.

Earlier this month, the joint meeting of the British Societies for Cell and Developmental Biology and the Japanese Society for Developmental Biology took place at the University of Warwick. A full report is in progress, but you can already have a look at the collection of tweets from the meeting, and an interview with Beddington Medal winner Boyan Bonev.

Lauren Killip attended the Canadian Developmental Biology Conference in Banff.

Also on the Node:
-Philip Washbourne describes how his lab worked with GeneTools to develop and optimize photo-morpholinos for use in zebrafish.
-You voted for a Development cover and chose an image of a skate. More to come soon.
-Kim Cooper is doing field work in China to collect jerboa embryos to study limb development.
-Erin Campbell gives the backstory about an image that demonstrates how stem cells are kept in place in the Drosophila germline niche.

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Although there was no “official hashtag” to be used on Twitter, several attendees of the recent BSCB/BSDB/JSDB meeting were livetweeting the event. I tried to keep up, and collected several of the tweets in this Storify, so you can see what was discussed online during the conference. A full report from the meeting is on its way as well.

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