Review on Michael’s Domain

Do fish have lymphatics?

Sat, 27 Jan 2024 00:00:00 +0000

Read the whole back story in our preprint: https://doi.org/10.20944/preprints202312.2119.v1 . It isn’t easy to believe that the scientific community cannot agree on whether zebrafish have a lymphatic vascular system. Zebrafish is one of the most successful model organisms in biology, and one would assume that we know its overall vascular setup. However, starting with W. Vogel in 1981 ( https://doi.org/10.1515/znc-1981-5-627 ), many fish physiologists subscribe to the notion that there are no lymphatics in fish, and most contemporary fish physiology textbooks have appropriated this point of view. At the same time, solid publications from multiple labs show that lymphatic vessels exist in fish ( https://doi.org/10.1038/nm1427 , https://doi.org/10.1016/j.cub.2006.05.026 ). What is going on? When the Yaniv lab published in 2022 that embryonic lymphatics in zebrafish can transdifferentiate into blood vessels ( https://doi.org/10.1038/s41586-022-04766-2 ), it suddenly appeared possible to unite the two contradictory views. In a nutshell: In most fish, an embryonic lymphatic system transdifferentiates during development into blood vessels that form a specialized subcompartment of the cardiovascular system (the so-called secondary vascular system). The degree of transdifferentiation seems quite variable between fish species, and some vessels - notably the thoracic duct - might retain a hybrid phenotype.As so often is the case in top journals, the original article by Das et al. neither discussed the 100-year-old controversy nor the ramifications of its landmark findings. Even though Kari Alitalo and I did so in a short commentary ( https://rdcu.be/cOjJ0 ), more space is needed to do justice to the topic. Although the controversy about piscine lymphatics is far from settled, it appears important to record the current status of the discussion in the scientific literature. Moreover, we wanted to describe a high-likelihood consensus model against which to plan future experiments. The result is an extended review; we hope you’ll enjoy reading it. If you find something that you don’t like, by all means, let us know! Especially if you can back up your critique with data or sound arguments. We sent the manuscript for review and are happy to improve it based on your input.

Review: Wenger Synergy rucksack after 5 years of daily use

Sat, 21 Jan 2023 00:00:00 +0000

I am a fan of rucksacks with many pockets. No wonder I like the Wenger Synergy , which has been on the market for over 10 years with only minor modifications. However, I had my fair share of quality issues with this model. Unlike my >40-year-old Swiss knife, this rucksack kept breaking within its warranty period or soon after. It was never a problem exchanging it when it broke within the warranty period, but I got fed up with the exchange hassle after doing it twice. The rucksack’s failing part was always the same: the seams of the shoulder straps started to open. I reported the issue directly to the producer, hoping they would change something to improve the shoulder straps. However, when also the third rucksack developed the same problem, I decided not to exchange it but to fix it. My fix is optically not very pleasing, but it has lasted long enough that I can report the second point of failure: the bottom pane. It ripped where the bottom piece contacts the backplane of the rucksack. I also repaired that one because I was interested in which part would fail next. The upside: these repairs were quick and easy, and they have already lasted for 4 months without any sign of failure due to the high-quality material. The zippers limit the ultimate lifetime of perhaps all rucksacksNow I know: the zippers are starting to have problems. I am surprised that the zippers are still sort of working. The zippers have been the Achilles heel with almost all of my other rucksacks. And unlike a shoulder strap, it takes quite an effort to fix (= exchange) a badly failing zipper. This rucksack is now five years old. I have been using it literally every single day. I cycle or run with it to work, and I do my shopping with it. I travel with it and take it to the summer cottage. Am I expecting too much of a ~100€ rucksack? Is five years’ lifetime the maximum I can get out of a rucksack these days? Sustainability is mostly just lip service, whatever the industry. I am determined to keep this rucksack for another 5 years, but exchanging the zippers will cost me at least 2 to 3 hours of work. As a quick fix, I used pliers to tighten the top and bottom wings of the metal slider (like in this youtube video ). That has been working, but according to my experience, this tightening needs to be repeated in increasingly shorter intervals, and finally, the metal will break. To avoid replacing the whole zipper, you can add buttons to create a new closure , which is perhaps less work if you are not very skillful at sewing.

KLK3: tumorigenic or not?

Wed, 22 Dec 2021 00:00:00 +0000

We have just published our latest review about the role of KLK3 as an activator of VEGF-C and VEGF-D in prostate cancer . Prostate cancer is one of the most common cancers in males. It is not a question of whether you will get it but only when. Once you reach your 80s, the likelihood of you having prostate cancer is bigger than not having it. In a 2013 autopsy study of Japanese males , who died of other causes, 59% of those older than 80 had prostate cancer. It is likely that many of these cases were indolent and would never have caused any problems. Only a few of them might have become symptomatic had these men lived longer. So, there is a significant interest in distinguishing those cancers that are going to cause problems. Many prognostic markers have been proposed to do exactly that: to predict which cancers would become problematic.From the vascular biology point of view, angiogenesis and lymphangiogenesis are two hallmarks of cancers that have been previously proposed to have prognostic value. When we stumbled upon the fact that prostate-specific antigen (PSA, also known as KLK3) is able to activate VEGF-C and VEGF-D , we thought that this might have significance for prostate cancer. Meanwhile, further research has clarified some questions, and it really seems to be that both VEGF-C and VEGF-D are involved in cancer progression. it is not clear yet which proteases are responsible for the activation of VEGF-C and VEGF-D in real human cancers. KLK3- or Cathepsin D (CTSD)-activated VEGF-D might be a possible cause of the resistance of tumors to bevacizumab (Avastin) treatment. The consequences of VEGF-C activation, on the other hand, are more difficult to predict because activated VEGF-C does simultaneously both good and bad: On the one hand, it facilitates metastasis. On the other hand, it enables an enhanced immune response against the tumour. Interesting research lies ahead. Read more in our review: https://doi.org/10.3390/ijms222413545

Minireview about key molecules in lymphatic development, function, and identification

Fri, 08 Jun 2018 00:00:00 +0000

Erich Brenner asked us more than a year ago whether we could contribute to the special issue about human lymph vessels he was editing for Annals of Anatomy. We agreed that we might be able to contribute a minireview. In the beginning, I was also hesitating, because Annals of Anatomy is not per se an open access journal. However, our university has meanwhile started to cover the article processing charges (APCs) for several publishers (including the biggest scientific publisher on this planet - Elsevier ) to make articles open access . Thus, everybody can not only read the article already now, but also share, copy and redistribute it, remix, transform, and build upon it for any purpose, even for commercial purposes as long as we - the original authors - are credited.The target audience is not the lymphatic research community, but outsiders, who need a first, very brief introduction to the molecules that are most central to the molecular biology of the lymphatic system. The selection is clearly biased by our own research history. Please write us an angry e-mail if we did not include your pet protein! If you convince us that your pet protein is central to lymphatic development or function, we’ll include it in our next review!

VEGF-C Review in Frontiers in Bioengineering and Biotechnology

Mon, 12 Feb 2018 00:00:00 +0000

The editors of Frontiers in Bioengineering and Biotechnology, section Tissue Engineering and Regenerative Medicine (Andrea Banfi, Wolfgang Holnthoner, Mikaël M. Martino and Seppo Ylä-Herttuala) asked us to contribute to the research topic Vascularization for Regenerative Medicine. We wrote a small review about VEGF-C, which specifically addresses the molecular biology of VEGF-C in relationship to regenerative medicine, i.e., (re)growing lymphatic vessels in vitro or in vivo.You can get it from the publisher directly https://www.frontiersin.org/articles/10.3389/fbioe.2018.00007/full or from here . **UPDATE (April 1, 2023):**The question of whether Frontiers Media is a predatory publisher did not even cross our minds when we were asked to contribute with a review. I know the guest editors of this Research Topic and can vouch for their scientific integrity. However, the journal has recently ended up on the list of predatory journals ( https://predatoryreports.org/news/f/list-of-all-frontiers-media-predatory-journals ), and the issues are discussed here in detail. Our review has meanwhile gathered:

No interest (in retrospection and introspection)?

Fri, 17 Feb 2017 00:00:00 +0000

There was much talk about last years “changes” at the university. Surprisingly, nobody seems to be interested anymore in the topic. At least this is the impression that I first got, when I went to the public hearing event at the Meilahti campus. The lecture hall 1 of Haartman Institute, where the hearing was supposed to take place, was completely empty when I arrived. Because only a handful of people had bothered to show up, the hearing had been moved to a table in the nearby Cafeteria. Hardly noticed by anyone, a review group has started its work to analyze the “changes” at the University of Helsinki, which took place during the last one and a half years. I guess the idea was to figure out what preventable mistakes have been done. According to this university source , Jukka Kola, who is the public face for many of the controversial decisions during this period, got to decide himself about the members of the review group. Because of this, the review group will have to be very careful not to appear biased in their report.

Review of GE Healthcare's Äkta Avant 25

Wed, 02 Mar 2016 00:00:00 +0000

About one year ago, we secured funding in an internal faculty call to replace the old Pharmacia Äkta Explorer 100 FPLC machine of the Protein Production and Purification core facility . The Äkta Explorer had been purchased in 1996(?) when the Swedish brand Pharmacia still existed. In 2014, the worse case scenerio happened and both monochromator and Xenon flash lamp broke almost simultaneously, which left us with a bill of almost 10000€. Hence we wanted to replace the machine with a contemporary model. There are only two companies offering serious devices in this space, which is GE Healthcare ( Äkta product line ) and BioRad ( NGC product line ). GE Healthcare inherited the Äkta brand from Pharmacia via multiple mergers, while BioRad is a relatively new contender with their NGC models, which they released only a few years back.We opted for the Äkta Avant 25 . We definitely wanted to have a cased, refrigerated fraction collector. And we wanted to have a familiar user experience. We often run automated purifications and we do not like our proteins to be for longer times at room temperature in open tubes into which bacteria and dust from the air can enter.By now, we have operated the Äkta Avant for about half a year and we have meanwhile a good idea how it compares to the Äkta Explorer. Even though the Avant is more modern than the Explorer, all users of our core facility still use the Explorer. They are familiar with the user interface of Unicorn 5.11 and seemingly have no interest in learning the - admittedly - more complicated UI of the Avant. But the other reason it was only in internal use so far was the fair amount of problems that we have encountered. With our old Äkta Explorer, we have never seen so many problems in such rapid succession. I don’t know whether our situation is typical (according to GE Healthcare’s representatives it is not). Nevertheless, here are the issues that we encountered: