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The sea anemone Nematostella vectensis is potentially immortal. Using molecular genetic methods, developmental biologists led by Ulrich Technau from the University of Vienna have now identified possible candidates for multipotent stem cells in the sea anemone for the first time. These stem cells are regulated by evolutionary highly conserved genes, which in humans are usually only active in the formation of egg and sperm cells, but give ancient animal phyla such as cnidarians a high degree of regenerative capacity to even escape aging. The results are published in Science Advances and could also provide insights into the human aging process in the future. While humans and most vertebrates can only regenerate parts of certain organs or limbs, other animal groups have far stronger regeneration mechanisms. This ability is made possible by pluripotent or multipotent stem cells, which can form (differentiate) almost all cell types of the body. https://lnkd.in/gRC3jaEY

☑️ *READ ASTRACT BELOW:* Prairie voles show strong pair bonding with their mating partners, and they demonstrate parental behavior toward their infants, indicating that the prairie vole is a unique animal model for analysis of molecular mechanisms of social behavior. Until a recent study, the signaling pathway of oxytocin was thought to be critical for the social behavior of prairie voles, but neuron-specific functional research may be necessary to identify the molecular mechanisms of social behavior. Prairie vole pluripotent stem cells of high quality are essential to elucidate the molecular mechanisms of social behaviors. Generation of high-quality induced pluripotent stem cells (iPSCs) would help to establish a genetically modified prairie vole, including knockout and knock-in models, based on the pluripotency of iPSCs. Thus, we attempted to establish high-quality prairie vole-derived iPSCs (pv-iPSCs) in this study. We constructed a polycistronic reprogramming vector, which included six reprograming factors (Oct3/4, Sox2, Klf4, c-myc, Lin28, and Nanog). Furthermore, we evaluated the effect of six reprogramming factors, which included Oct3/4 with the transactivation domain (TAD) of MyoD. Implantation of the pv-iPSCs into immunodeficient mice caused a teratoma with three germ layers. Furthermore, the established pv-iPSCs tested positive for stem cell markers, including alkaline phosphatase activity (ALP), stage-specific embryonic antigen (SSEA)-1, and dependence on leukemia inhibitory factor (LIF). Our data indicate that our newly established pv-iPSCs may be a useful tool for genetic analysis of social behavior. Katayama M, Cell Transplant. 2016;25(5):783-96. doi: 10.3727/096368916X690502. Epub 2016 Jan 15. PMID: 26777120. #Gesundheit #Bildung #Fuehrung #Coaching #Mindset #Motivation #Gehirn #Neuroscience #Psychologie #Persoenlichkeitsentwicklung #Kindheit #KeyNoteSpeaker #Humangenetik #Biochemie #Neuroleadership #Ernaehrung #Transformation #Stress #Demografie #Gender #Age #interkulturelleKompetenz #Epigenetik #Veraenderung #EmotionaleIntelligenz #Change #Gesellschaft #Organisationsentwicklung #Philosophie #Beratung # Quantum

Would you like some free reagents for insect biology research? In the human nervous system, the small glycoprotein Apolipoprotein D is strongly upregulated in aging, in nerve damage, and in neurodegeneration. Overexpression of Apolipoprotein D is also linked to obesity, diabetes, and cancer. Insects also have homologs of Apolipoprotein D, called Lazarillo. In my PhD work, we showed that blocking Lazarillo in grasshopper embryos prevented the axons of their neurons from growing to their targets. In flies, Lazarillo is strongly expressed during embryonic development as the nervous system is first forming, during pupal development as the nervous system is being rewired, and in the adult mushroom bodies, important brain centers for learning and memory. Diego Sanchez of Universidad de Valladolid has being doing research on Lazarillo / Apolipoprotein D for decades. For example, he showed that knocking out Lazarillo in glia in flies reduces their fat stores, degrades their ability to cope with starvation or oxidative stress, speeds up neurodegeneration, and makes them die younger: https://lnkd.in/eh2hrqQh Now Diego Sanchez is shifting his research focus to concentrate on Apolipoprotein D in mammals. He has reagents, such as antibodies, for investigating Lazarillo in insects. He's looking to give away these materials to other scientists. So if anyone might be interested in doing experiments with this glycoprotein, let me know, and I can put you in touch with him.

Excited to share the pre-print of the first story of my PhD project, investigating the function of peptidyl arginine deiminase 6 (PADI6), with Louise Walport at The Francis Crick Institute. PADI6 is a maternal factor that is crucial for early embryo development in mice and humans, with loss-of-function variants or gene knock-out resulting in female infertility. Part of the PADI family of enzymes, that catalyse the post-translational conversion of arginine to citrulline, PADI6 is the odd one out. It is less conserved with the other PADIs than they are with each other, and there is currently no reported catalytic activity of PADI6. As part of my PhD, we aimed to structurally and biochemically characterise PADI6 to determine what effect this lack of conservation has on its structure, and understand why PADI6 doesn't have any catalytic activity in standard in vitro assays. First, we validate reported data that human PADI6 (hPADI6) is inactive in vitro against common PADI substrates. We show it dimerises like PADIs 2 to 4, and that it does not bind calcium ions. With Stéphane Mouilleron of The Francis Crick Institute, we then determined a 2.44 Å X-ray crystal structure of wild type hPADI6. While this manuscript was in preparation, a hPADI6 phosphomimic mutant (V10E/S446E) structure was published (DOI: 10.1107/S2052252524002549), aligning well with our structure, and validating our biochemical assays. With our structure we identify a unique loop, not present in the other PADIs, that holds the active site pocket closed, providing insight into the apparent lack of catalytic activity of PADI6. This loop is highly conserved in the PADI6 sequence of 80 species suggesting a unique evolved mechanism by which the PADI6 active site is blocked. Finally, with Professor Joe Marsh of the University of Edinburgh, we use our structure to model the biallelic structural damaging effect of clinically significant variants reported to cause infertility and multi-locus imprinting disorders (MLID). Variants that result in infertility have a significantly higher biallelic damage score than those that result in MLID, or control variants, suggesting that hPADI6 structural damage is the primary molecular mechanism underlying infertility-associated missense variants. https://lnkd.in/ejEJUxQK

Cryopreservation of Gametes and Embryos and Their Molecular Changes: Cryopreservation process can lead to molecular changes and potential damage in both gametes and embryos. Methods of Cryopreservation: 1. Slow - Freezing 2. Vitrification Both vitrification and slow-freezing methods aim to prevent ice formation in cells, but they utilize different techniques. Vitrification tends to yield higher survival rates for gametes and embryos compared to slow-freezing. Nonetheless, both methods can negatively influence cell metabolism and viability. Molecular Changes in Cryopreserved Embryos: (1)Cellular Changes: Mitochondrial function is altered, and oxidative stress levels increase. (2)Proteomic Changes: The expression of proteins related to metabolism and apoptosis is affected. (3) Epigenetic Changes: There are notable alterations in DNA methylation patterns and histone modifications. (4) Transcriptomic and Genomic Changes: Gene expression that influences cell survival is impacted. (5) Effects on Offspring: These changes may have long-term implications for growth and metabolic function. Molecular Changes in Cryopreserved Oocytes: The cryopreservation of oocytes also results in several alterations: (1) Cellular Changes: Cryoprotective agents (CPAs) can disrupt calcium balance and mitochondrial function. (2) Proteomic Changes: Particularly with slow-freezing, there is a significant alteration in protein expression. (3) Epigenetic Changes: Although research is limited, there have been observed changes in DNA methylation. (4) Transcriptomic and Genomic Changes: Vitrification appears to affect gene expression related to embryo development. Molecular Changes in Cryopreserved Sperm: (1) Cellular and Proteomic Changes: There is an increase in oxidative stress, DNA damage, and impaired motility. (2) Epigenetic Changes: This process can lead to DNA fragmentation and chromatin remodeling. (3) Genetic and Transcriptomic Changes: Gene expression essential for sperm function and fertilization is altered. Future Perspectives: Ongoing research is focused on developing new methodologies to enhance cryopreservation outcomes. Current studies are exploring the use of antioxidants and innovative freezing techniques to mitigate the effects of cryopreservation. #Cryopreservation #AssistedReproductiveTechnology #IVF #Embryology #Embryologist #FertilityPreservation #Gametes #OocyteVitrification #MolecularBiology #Epigenetics #ReproductiveHealth #SpermCryopreservation #EmbryoFreezing #ClinicalEmbryology #FertilityScience #Biotechnology

N-terminal ubiquitination of mutated Huntingtin plays a neuroprotective role, promotes peripheral sequestration and delays neuronal death. Huntington’s Disease (HD) is an inherited progressive disease of the nervous system, caused by a mutation in the huntingtin gene (HTT). HD primarily affects the basal ganglia and is characterized mainly by uncontrolled movements (chorea) among other symptoms including motor, cognitive, and psychiatric decline. Our group (Boulos et al., 2024), has found that the mutated Huntingtin (mHtt) is gradually sequestered to peripheral, mainly axonal, aggregates whereas cytosolic mHtt levels decrease, subsequently enhancing neuronal survival in cortical rat tissues. We used long-term in situ pulse-chase imaging and showed that aggregates continually gain and lose mHtt, in line with these acting as mHtt sinks at equilibrium with cytosolic pools. Mutating two N-terminal lysine residues that undergo ubiquitination in HD animal models suppresses peripheral aggregate formation and reduces cytosolic mHtt, promoting nuclear aggregate formation and pervasive neuronal death. These findings demonstrate the capacity of aggregates formed at peripheral locations to sequester away cytosolic, presumably toxic mHtt forms and support a crucial role for N-terminal ubiquitination in promoting these processes and delaying neuronal death. #huntingtondisease #neurobiology #neuroscience #brain #pathophysiology #aggregation #protein #paper #mhtt #biology #science #academia

The thymus is central to T-cell maturation, safeguarding the body against pathogens while maintaining tolerance to its own tissues. This delicate balance is orchestrated by the thymic epithelium, which, in mammals, birds, and bony fish, originates from the third and/or fourth pharyngeal pouches during embryonic development. Intriguingly, other vertebrates rely on distinct pouches to form thymic primordia. My colleague and friend Hélia Neves has been exploring thymus development using a fascinating quail-chick chimeric in vitro model. For the first time, she observed that the second pharyngeal pouch can form thymus tissue as efficiently as the third—provided it interacts with the right tissues. To dive deeper into the molecular mechanisms driving this process, Hélia challenged me to collaborate on mapping the transcriptome of the embryonic regions involved and use it to unravel the signaling networks established between the pharyngeal arch mesenchyme and pouch endoderm. Our findings, based on experimental work conducted by Hélia, Isabel Alcobia and colleagues in the Edgar Gomes Lab at the (now Gulbenkian) Institute for Molecular Medicine (GIMM), and enriched by Domingos Henrique’s keen insights into developmental biology, reveal a conserved genetic program capable of inducing thymus development regardless of anatomical location. Notably, we identified the dorsal region of the second pharyngeal arch as a key inhibitor of thymus formation, highlighting how surrounding tissues influence the pouch endoderm's potential. These insights open new avenues for manipulating thymus development, particularly in regenerative medicine. The study will be featured in the December 24 🎄issue of Cell Reports, but it’s already available online. You can read it at: https://lnkd.in/dx52gZUY In addition to the exciting results, this work holds a special place in my heart, as it brought together a group of seasoned researchers whose journey goes back nearly 30 years to the Institute of Histology and Embryology at the Faculdade de Medicina da Universidade de Lisboa and even before that to the undergrad Biology course at Faculdade de Ciências da Universidade de Lisboa 😊 #transcriptomics #research BioISI - Biosystems & Integrative Sciences Institute

2024 was a year full of discoveries at IMBA! Our scientists published 55 manuscripts, more than one per week! Today, we look at some of this year’s research highlights. The Burga lab discovered a selfish genetic element that is silenced only when inherited paternally, a potential evolutionary origin for genomic imprinting.  https://lnkd.in/dSggZXTG The Tanaka group described chromatin “zip codes” that guide the axolotl’s cells to precisely regenerate the structure and functionality of their limbs. https://bit.ly/4gvwRrc The Brennecke lab identified the single amino acid responsible for the interaction between Rhino and Kipferl, two key proteins for piRNA expression and transposon silencing. The Rivron lab discovered a “pause button” that halts the development of blastoids, – early-stage embryo models – for up to 8 days. https://bit.ly/4gCMz4K The Penninger group showed that that the intestine reorganizes during pregnancy and breastfeeding to ensure proper feeding and nourishment of the ~~b~~baby. https://bit.ly/4gAasZI The Knoblich lab used brain organoids to replicate long-range brain connections and showed how ARID1B mutations disrupt the formation of the corpus callosum. https://bit.ly/3WrXt5u Read more about the science breakthroughs happening at IMBA here: https://bit.ly/4fezpZE

🪰 Watch the Mitosis of a Fruit Fly Embryo! The 2024 Nikon Small World in Motion video winners have been announced, and as always, the results are stunning. Now in its 14th year, this international competition highlights the best microscopy videos from hundreds of entries, each offering a unique glimpse into the microscopic world. 🔬 Dr. Bruno Vellutini's winning video showcases the mesmerizing waves of cell division and tissue movement, vital for the proper development of fruit fly embryos. This footage is not just beautiful — it holds critical insights into genetic pathways that are mirrored in humans and other mammals, with major implications for cancer research, birth defects, and new treatment development. 🧬 Follow @Science for continuous discovery! #science #biology #mitosis

Scientists Accidentally Made a Mouse Grow Legs in Place of Genitals 07 April 2024 By TESSA KOUMOUNDOUROS Photo: Scan of six limbed mouse embryo with limbs highlighted, extras in magenta (Lozovska et al., Nat. Comms, 2024) Turning off a gene early in mouse development led researchers to end up with an accidental six-legged embryonic mammal. This strange result took the spinal cord research of developmental biologists Anastasiia Lozovska and Moisés Mallo and their colleagues at Portugal's Gulbenkian Science Institute in a new direction. "I didn't choose the project, the project chose me," Mallo told Sara Reardon at Nature News. The team compared 10 to 17-day-old mouse embryos with and without functioning versions of the gene in question, Tgfbr1, which codes for the Tgfbr1 receptor protein. Tgfbr1 contributes to a signaling pathway that gives a forming body its trunk-to-tail directions. This pathway provides a 'create a hindlimb' here, or 'external genitals' instructions to the developing embryo's cells. While legs and arms share many of the same genes, this early in the process, the hindlimbs and genitals have more in common. There has been some suggestion they arise from the same initial primordium structure in ancestral species.