For most of us, we don’t all end up settled as adults in the same town where we were born.  The same is true for many cells, including some stem cells in the fruit fly intestine.  A recent paper describes the migration of progenitor cells, some of which will later become stem cells, in the intestine of developing flies, with the help of stunning images of these boundary-crossing cells.

Adult stem cells divide and differentiate to compensate for cell loss or cell injury in adult tissue.  Understanding where these adult stem cells originate during development and how they migrate to their final position in adult tissue is an important question in stem cell biology.  A recent paper in Development describes the migration of Drosophila intestinal stem cells during metamorphosis.  Takashima and colleagues traced the migration of progenitor cells in the intestine—in the midgut, hindgut, and the excretory Malpighian tubules.  A subset of adult midgut progenitors migrates posteriorly to form the adult ureters, and in later pupal stages these progenitors migrate to the Malpighian tubules to give rise to renal stem cells.  These results establish, for the first time, the origin of the renal stem cells in Malpighian tubules.  Conversely, during early pupal development a subset of hindgut progenitor cells migrates anteriorly, with these presumptive stem cells later differentiating into midgut enterocytes.  Takashima and colleagues found that Wingless helps regulate the balance of hindgut progenitors that differentiate into midgut or hindgut enterocytes.  These results show that the boundary between the midgut and hindgut regions is not stable until later in development.  Pluripotent progenitor cells are able to cross this boundary and adopt the fate of their new domain.  In the image above, hindgut progenitor cells (green) are found in the hindgut-midgut boundary (the hindgut proliferation zone, HPZ).  Early in development, hindgut progenitor cells were lineage traced and later show their migration across the HPZ and toward the midgut (lineage traced cells in red).

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.
Takashima, S., Paul, M., Aghajanian, P., Younossi-Hartenstein, A., & Hartenstein, V. (2013). Migration of Drosophila intestinal stem cells across organ boundaries Development, 140 (9), 1903-1911 DOI: 10.1242/dev.082933

(1 votes)

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Continuous supply of mature differentiated cells by adult stem cells is required in most of adult tissues especially those with rapid turnover rates. In recent years, using advanced cell biological methods, many studies have uncovered homeostatic mechanisms that are driven by specific tissue resident stem cells. Mammalian lingual epithelium (tongue) always had been a focus for identifying diverse taste receptors, cells and their mechanism of action. However, stem cells for this high turnover tissue remained largely uncharacterized. In a recent study published in Nature Cell Biology, Tanaka et al., show how homeostasis and regeneration of lingual epithelium are maintained by distinct stem cell population.

Mammalian tongue is composed of taste buds and keratinized epithelial cells, the later providing rigidity for the organ. The authors of this study attempted to identify stem cells that generate these differentiated epithelial cells. They combine the knowledge of classical thymidine labeling studies and state-of-the-art multicolour cell lineage techniques. It has been proposed previously that the keratin 5/14 positive lingual epithelial cell population possesses characteristics of stem cells. Authors of this work proved that these cells were not a distinct population of cells that gives rise to differentiated cells, however the stem cells they have identified do express these markers. To identify the individual population origin of differentiated cells, they labeled cells with CreERT2-inducible multicolour fluorescent reporters (green, blue, orange, red). They identified few label retaining cells after 28 days at the interpapillary pit (IPP) of the lingual epithelium. To identify a specific marker within this small population of cells, they have crossed various stem cell marker-CreERT2 knock-in mice with the multicolour expressing rainbow mice and confirmed Bmi1 (Bmi1 polycomb ring finger oncogene) as a lingual stem cell marker! Previously, Bmi1 has been reported as intestinal stem cell marker. There is no obvious explanation on how they chose Bmi1 as a likely candidate (cherry pick?!). However, further experiments with RNA in-situ hybridization proved the highest expression of this gene in lingual epithelial stem cells. Taste bud cells were not labeled long-term in Bmi1^CreER/+/Rosa26^rbw/+ mice confirming that the Bmi1-positive cells identified are unipotent stem cells giving rise to keratinized epithelial cells.

Furthermore, to examine the regenerative capacity of Bmi1-positive stem cells, the authors injured the lingual epithelial cells with different doses of irradiation. Progeny of Bmi1-positive cells were detected on the surface of keratinized epithelial cells at day 7 after irradiation and regenerated the injured tissue. To analyze the regenerative ability in the absence of Bmi1-positive cells, they have effectively deleted Bmi1-positive cells by crossing Bmi1^CreER/+ mice with Rosa26^{loxp–stop–loxp–dta/+} mice. In this system, Tamoxifen induction of CreERT2 trigger the expression of Diphtheria toxin (DTA) which kills the cells. Removal of Bmi1-positive cells leads to decreased proliferation of basal cells, proving the hypothesis that the Bmi1-positive cells play a role in tissue regeneration.

The authors conclude that the Bmi1-positive cells are slow cycling long-term stem cells, giving a hint to hunt for rapid proliferating stem cell population in lingual epithelium, which is not identified yet. Also, further investigations on the role of Bmi1-positive cells in lingual origin of squamous cell carcinoma would allow targeting this gene for therapeutic interventions.

 
Tanaka T, et al., Identification of stem cells that maintain and regenerate lingual keratinized epithelial cells. Nature Cell Biology. 2013 May;15(5):511-8.

(3 votes)

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The lab can be one of the greatest places in the world to make live long friends. Spending countless hours in a tissue culture room late into the middle of the night, sharing similar frustrations when experiments don’t work or talking about how your PI does not have a clue what they are talking about can really bring people together. This is also compounded by the fact that you will spend some of the most formative years of your life with these people. They’ll be the first people you see in the morning, the last people you see at night, and the people that you will spend most of your time socialising outside of the lab with.

However, pressure in every profession can push people to the edge and increase tensions between lab members and in some cases result in bullying. Unfortunately, education does not prevent bullying from occurring in academia and is sadly somewhat a regular occurrence within labs and surprisingly is still found to occur at the higher levels among faculty members.

For PhDs and Post-Docs the constant pressure to perform both technically and mentally can be a lot to handle. In some cases this can get the best of people, with envy being a consuming emotion that results in tension between lab members. Resenting other people in the lab due to their success no matter how big or small can result in the abuse or coercion of others and in some extreme cases result in bully’s tampering with their victims work and stealing their supplies.

Intimidation from other lab members is not the only place where this mental torture comes from, with many PI’s being some of the biggest bully’s within academia. On many occasions I have watched group leaders shout openly at their students, berate their work and on more than one occasion throw their lab book out the window.

One post-doc that I use to work with would go MIA for a few days after meeting with the PI, just to relieve the tension within the lab.  Another lab beside me would orientate a magnet on their freezer in a certain way to represent whether the PI was in or not, so much was the fear of dealing with her. On another occasion a PhD student friend of mine suffered intimidation for months from her PI and eventually was fired without cause. When they approached the HR department within the college they were told that the Professor was ‘too powerful’ and the college could do nothing to resolve their cause, leaving them with no choice but to leave quietly.

If you are suffering from bullying within the lab or know someone who is, directing them towards your university counselling service can always help. If not, lending a helpful ear or discussing your problems with a member outside of the lab might help them/you see the bigger picture and allow you get confront the problem.

www.postpostdoc.com

(5 votes)

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Hi! My name is Cat and I am the new Community Manager here at The Node. I am originally from Portugal, but moved to the UK to study a long time ago (almost a decade!). Until very recently I was a PhD student at Jordan Raff’s lab in Oxford, using fruit flies to study how centrosomes are formed- so I like to think of myself as a cell biologist with a developmental twist! Although I had a great time in the lab, I eventually realized that I enjoyed much more interacting with scientists and hearing about their science than doing my own…

This is why I am so excited about my new position as The Node Community Manager- in its essence, The Node is a place to bring scientists (you!) together, to share ideas and opinions and the latest research. I want to play my part in facilitating that! Eva did an excellent job in setting up and developing The Node in the last three years, and that is a hard act to follow. Going forwards, I will do my best to continue making The Node the vibrant and dynamic community website that it is, and you’ll be hearing a lot more from me in the coming months. Meanwhile, please continue to contribute content and comments to The Node, and do not hesitate to contact me if you have any suggestions, questions or comments. You can drop me an email at thenode [at] biologists.com (or by clicking here) and please do say hello if you see me at a conference. I look forward to meeting you!

(11 votes)

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Here are the highlights from the new issue of Development:

Sniffing out sensory maps

The development of sensory maps – neural representations of the sense organs – involves the growth of sensory nerve axons into specific regions of the brain and the formation of precise synaptic connections. On p. 2398, Jean-François Cloutier and colleagues investigate the molecular mechanism that underlies the coalescence of vomeronasal sensory neuron (VSN) axons into discrete synaptic units, termed glomeruli, in the mouse accessory olfactory bulb (AOB), which is involved in processing signals that control social and sexual interactions. The researchers report that the transmembrane proteins Kirrel2 and Kirrel3 are differentially expressed in subpopulations of VSNs and show that Kirrel3 expression is required for the coalescence of axons into glomeruli. Specifically, the posterior AOB in Kirrel3^−/− mice contains fewer, larger glomeruli than the AOB of wild-type mice. Moreover, Kirrel3^−/− mice display reduced male-male aggression. The researchers propose, therefore, that differential expression of Kirrels on VSN axons generates a molecular code that is required for the proper coalescence of these axons into glomeruli within the AOB.

Tip-top role for SRF in angiogenesis

The evolutionarily conserved transcription factor SRF (serum response factor) is involved in several developmental processes that require cell migration, including embryonic angiogenesis. Here (p. 2321), Zhenlin Li and colleagues investigate the function of SRF during postnatal angiogenesis. They show that the inducible, endothelial-specific deletion of Srf in postnatal mice reduces postnatal growth and viability, induces systemic hypovascularisation and retinal angiopathy, and decreases angiogenesis in implanted tumours. Genetic mosaic analysis indicates that defective filopodia formation by the tip cells of angiogenic sprouts and reduced cell contractility are the primary causes of these angiogenic defects. The researchers also show that VEGFA induces nuclear accumulation of myocardin-related transcription factors (MRTFs; co-factors that regulate the transcriptional output of SRF) and that MRTF-SRF activity controls the expression of contractility genes that are important for endothelial cell migration. The researchers conclude that SRF regulates tip cell invasive behaviour during sprouting angiogenesis and hypothesize that curbing pathological angiogenesis by targeting the SRF pathway might restrict tumour growth.

Pygopus, chromatin and Wnt signalling

The mouse genome contains two genes for Pygopus (Pygo), which was identified as a Wnt signalling component in Drosophila. All Pygo proteins contain a conserved plant homology domain (PHD) that allows them to bind di- and trimethylated lysine 4 on histone H3, but is histone binding required for Pygo to function in Wnt signalling? To investigate this question, Konrad Basler and colleagues have generated mice homozygous for a Pygo2 mutation that abolishes chromatin binding (p. 2377). Surprisingly, Pygo2-chromatin binding is not needed to maintain Pygo2 function during mouse development, and abrogation of the Pygo2-chromatin interaction has little effect on Wnt signalling-related transcription during tissue homeostasis. Compromised Pygo2-chromatin binding leads to male sterility, however, and the researchers report that PHD-dependent recruitment of Pygo to regulatory regions in the testes is important for the recruitment of the histone acetylase Gcn5 to chromatin. These results identify a testis-specific role for Pygo2 as a chromatin remodeller that is unrelated to its role as a modulator of Wnt signalling.

Tumours and embryos tread the same path

Tumour cells share many characteristics with embryonic cells and it is thought that they acquire these characteristics through activation of developmental pathways. On p. 2354, Leonard Zon and co-workers develop a screening strategy to look for pathways that are common to embryogenesis and tumorigenesis in zebrafish. The researchers first evaluate gene expression in transgenic zebrafish embryos that express an inducible mutated RAS gene – RAS family members are the most commonly mutated oncogenes in human cancers and the RAS pathway is a key developmental pathway during embryogenesis. The researchers then use one of the genes that is upregulated by RAS expression to screen for small molecules that interfere with RAS signalling during embryogenesis. Finally, they show that two of the retrieved inhibitors suppress the growth of a zebrafish KRAS-induced embryonal rhabdomyosarcoma and of an NRAS-induced human rhabdomyosarcoma cell line. Together, these results demonstrate that common pathways are activated by RAS during embryogenesis and tumorigenesis and establish zebrafish embryos as a platform for anti-cancer drug discovery.

Neural crest segregation out-Foxed

Fate segregation of multipotent progenitors is a key developmental process. The neural crest, which generates numerous cell types, is an ideal system in which to investigate this process. On p. 2269, Chaya Kalcheim and co-workers investigate when and how neurogenic and melanogenic neural crest cells segregate. Previously, the researchers reported that, even before emigration from the neural tube, neural but not melanocyte progenitors express the transcription factors Foxd3, Sox9 and Snail2. Now, they show that avian melanocytes are initially part of the Foxd3-positive premigratory epithelium but downregulate Foxd3 before emigration from the neural tube. If Foxd3 downregulation is prevented, avian melanocyte progenitors fail to upregulate the melanogenic marker Mitf and the guidance receptor Ednrb2. Consistent with these data, loss of Foxd3 function in mouse neural crest results in ectopic melanogenesis in the dorsal tube and sensory ganglia. The researchers propose, therefore, that Foxd3 is part of a dynamically expressed network of neural tube genes that regulates the segregation of neurogenic and melanogenic neural crest cells.

Elastic fibres form early in human cardiac valves

Cardiac semilunar valves, which stop blood leaking back into the heart, contain an elastic fibre network that is essential for their physiological function. Histochemical studies suggest that this network, which contains elastin, fibrillins, linking proteins such as fibulins, and fibronectin, is not crucial for early human cardiac valve development. Here (p. 2345), Katja Schenke-Layland and colleagues challenge this assumption by systematically analysing elastogenesis in human semilunar valves. The researchers report that the transcription of genes essential for elastic fibre formation starts early within the first trimester of pregnancy. Using immunohistochemistry, they show that fibronectin, fibrillins and linking proteins are present at the onset of cardiac cushion formation (about week 4 of development) and that tropoelastin/elastin protein expression is first detectable in the valves at about week 7 of pregnancy, the stage of development when the embryo’s blood pressure and heartbeat increase. Together, these findings suggest that elastogenesis is important for the development of functional semilunar valves.

PLUS…

The neural crest

Roberto Mayor and Eric Theveneau provide an overview of neural crest formation, differentiation and migration, highlighting the molecular mechanisms governing neural crest migration.

See the Development at a Glance poster article on p. 2247

Polar auxin transport: models and mechanisms

Spatial patterns of auxin are important drivers of plant development. Here, ten Tusscher, Scheres and colleagues present a mathematical analysis of published models of auxin transport and suggest that current models alone cannot explain the auxin patterns found in plants. See the Hypothesis article on p. 2253

(1 votes)

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Department: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR

Salary: £37,382 – £63,535

Closing Date: 1st July 2013

The Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute is a world-leading centre for research in stem cell biology and medicine, based in central Cambridge and at the Biomedical Research Campus (http://www.stemcells.cam.ac.uk )

The Institute is seeking new Group Leaders at both junior and senior level to complement and extend our existing programmes. Areas of interest include: (i) physical biology and bioengineering of stem cells; (ii) stem cell-based disease modelling and regenerative medicine; (iii) adult tissue stem cell biology.

Our mission is to make fundamental discoveries in stem cell biology and translate them into biomedical applications. We therefore particularly welcome applications from individuals with interest in bridging between basic research and medical applications.

Junior Group Leader candidates will have substantial post-doctoral experience with demonstrable research success and an original research proposal. Senior Group Leader candidates will have an established reputation for independent high quality research.

The Institute offers excellent core facilities for stem cell culture, ES cell transgenesis, flow cytometry, imaging, and bioinformatics. Successful candidates will be supported to obtain external personal fellowship and grant support within 1-2 years.  A generous interim start-up package is available. Depending on experience, you can expect remuneration between £37,382 – £63,535.

Informal enquiries are welcome and may be addressed to the Director, Professor Austin Smith (agssec@cscr.cam.ac.uk) or any member of the Institute Steering Committee (http://www.stemcells.cam.ac.uk/about-us/governance/ ).

Applications should be submitted using the online application http://www.stemcells.cam.ac.uk/careers-study/vacancies/.  Applicants should upload a CHRIS 6, (http://www.admin.cam.ac.uk/offices/hr/forms/chris6/). a full curriculum vitae and 1-2 page outline of research interests, by 1700 (GMT) 01 July 2013.

Interviews will be held on 3rd and 4th October 2013. If you have not been invited for interview by 25th September 2013, you have not been successful on this occasion.

The University values diversity and is committed to equality of opportunity.

(No Ratings Yet)

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Department: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR

Based at: Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, West Forvie Building, Robinson Way, Cambridge, CB2 0SZ

Salary: £27,854-£36,298 pa

Closing Date: 9th June 2013

Fixed Term: Funds for this post are available until 30th June 2017 in the first instance

The Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute (SCI) comprises 200 researchers spanning fundamental science through to clinical applications. Our goal is to advance disease modelling, drug discovery and regenerative medicine through understanding the genetic and biochemical mechanisms that control stem cell fate.

We are seeking an enthusiastic and highly motivated person to join the Anne McLaren Laboratory for Regenerative Medicine at the Biomedical Research Campus (Addenbrooke’s Hospital).  As the senior member of assistant staff, you will provide technical and administrative support to the Head of Translation Medicine; the main duties will include the procurement and maintenance of equipment and the implementation and compliance with Health and Safety at work legislation within the Laboratory. Prior experience in research environment is essential, experience in operating and maintaining highly specialist microscopy and flow cytometry is desirable.

The role holder will be responsible for the line management of the support staff and provide solutions as they arise.  You will provide clear leadership to the support team and have the ability to deal sympathetically and effectively with a wide range of people and issues, with excellent interpersonal and communication skills. Educated to degree level, candidates will need to have a friendly and positive manner and enjoy working with a range of people.

You will liaise with the SCI Principal Assistant when procuring high value equipment and consumables and liaise with the Central Biomedical Resource staff who are responsible for the buildings maintenance, safety and security of the building and its infrastructural equipment.  This role will require a high level of organisation, ability to communicate and motivate others excellent IT skills and competence in using Microsoft Office.  At times you may be required to work alone, or as part of a team, managing their own day-to-day workload.

To apply, please visit our vacancies webpage: http://www.stemcells.cam.ac.uk/careers-study/vacancies/

Informal enquiries are also welcome via email: cscrjobs@cscr.cam.ac.uk

Applications must be submitted by 17:00 on the closing date 9th June 2013.

Interviews will be held on Tuesday 25^th June 2013. If you have not been invited for interview by 21^st June 2013, you have not been successful on this occasion.

Please quote reference PS01219 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

(No Ratings Yet)

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Back in February, you voted on the first set of beautiful images taken by last year’s Woods Hole Embryology Course students, and this confocal picture of a mouse embryo appeared on the cover of Development last month. Now it’s time for the next round: please vote in the poll below for which of the following four images you would like to see on a future cover of the journal. To see bigger versions, just click on the image.

Voting closes noon GMT on May 21st

1. Confocal image (extended focus Z stack) of a Crepidula fornicata (slipper limpet) veliger larva. Stained with phalloidin (F-actin; purple), DAPI (cell nuclei, blue), anti-serotonin (yellow), and anti-acetylated tubulin (red). The shell (green) image was created from the DIC picture collected during the confocal scan. The C-shaped line of nuclei are cells at the edge of the velum; the acetylated tubulin (red) staining reveals the ciliated surface of the velum. The F-actin staining (purple) highlights the main larval retractor muscle. Serotonin (yellow) reveals the serotonergic neuron cell bodies and axons. This image was taken by Joyce Pieretti (University of Chicago), Manuela Truebano (Plymouth University), Saori Tani (Kobe University) and Daniela Di Bella (Fundacion Instituto Leloir).

2. Embryo of the dwarf cuttlefish, Sepia bandensis, stained with phalloidin (F-actin; green), DAPI (nuclei, blue), and anti Pax 3/7 (MAb DP312, red). The developing cuttlebone (purple) and eyes (yellow) were rendered using the DIC image collected during the confocal scan. The F-actin staining (green) reveals the developing musculature and brain, while Pax 3/7 (red) is expressed in a subset of neurons in the brain as well as two patches of epithelia in the mantle and portions of the arms and tentacles. The cuttlebone (purple) is a chambered, gas-filled internal shell made of aragonite that provides buoyancy control. Within each eye (yellow), the developing lens is seen as an internal sphere. Seven of the eight arms are visible along with the two tentacles that have sucker-covered ends. This image was taken by Maggie Rigney (University of Texas, Austin) and Nipam Patel (University of California).

3. The planarian, Dugesia sanchezi, immunostained for acetylated tubulin (green) and phospho-histone-H3 (dividing cells, purple). This individual has regenerated two heads. This image was taken by Chang Liu (Shanghai Institute of Biochemistry and Cell Biology).

4. Juvenile of the Longfin inshore squid, Loligo pealei, stained with anti-acetylated tubulin (green), phalloidin (F-actin, red), and Hoechst (nuclei, blue). The F-actin staining (red) reveals the musculature of the mantle; and the acetylated-tubulin staining (green) reveals the tufts of cilia on the surface of the mantle and rest of the body. This image was taken by Wang Chi Lau (Chinese University of Hong Kong).

(9 votes)

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Again, things have been busy on the Node this month and, as well as the usual flurry of job adverts, we’ve had some great research- and meeting-based posts.

Below are just some of the highlights. Remember – it’s easy to post on the Node, so feel free to get in touch (or simply post away!) if you have any developmental biology-related news, events or discussions that you’d like to share with the community.

Stem Cells Image Competition

The results of the competition were finally announced. Thanks to all of you who’ve submitted images and/or voted. Congratulations again to Lulu Xing of the University of Melbourne. Lulu’s  winning image (“The Garden of Memory”) will be appearing on a cover of Development in the coming weeks.

Research highlights

– We had our first “Journal Club on the Node” post – thanks to the University of Chicago Development, Regeneration and Stem Cell Journal Club for sharing their discussion with us. We look forward to seeing many more of these journal clubs – from U. Chicago and any other journals clubs that are interested – on the Node in the future.

– Patricia Gongal highlighted a recent Nature paper that used a clever approach to visualize retinoic acid gradients.

– Rachael Inglis highlighted a recent report of the discovery of some fossilised dinosaur embryos.

Journal/publishing news

– Our new Editor, Benoit Bruneau, explained why he’s so excited to be joining the journal.

– One of Development’s sister journals, Disease Models and Mechanisms (DMM), announced the appointment of a new team of academic editors.

– SpotOn, Nature Publishing Group’s online forum for science policy, outreach and tools, featured the Node as a case study for using social media in science.

News from meetings and conferences

– Continuing with the reports from the BSDB/BSCB Joint Spring Meeting, Andrei Luchici summarised Day 1 at the meeting. 

– Steff Knappe also painted an overview of some of the topics covered at the BSDB/BSCB meeting. You can also see the earlier report from Steff on the Careers Workshop.

– Robert Blassberg reported back from his recent trip to Japan during which time he attended the joint UK-Japan workshop on Neural Epigenetics, held at the British Embassy in Tokyo.

– If you’re interested in attending a hands-on dev biol course, read more about the upcoming International Course on Developmental Biology.

 Happy reading!

(No Ratings Yet)

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