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In the realm of academic publishing, a new and transformative platform is on the horizon - an open-access peer-reviewed platform known as Free Science. With a vision to revolutionize the way scientific research is shared and accessed, Free Science is set to provide a structured and inclusive space for researchers to submit their work, undergo rigorous peer review, and have their findings available to the public free of charge. This innovative platform, named Free Science, boasts a comprehensive array of features aimed at streamlining the publishing process. From a smooth submission system to efficient peer review workflows, editorial management tools, and an open access repository, Free Science is committed to enhance collaboration and advancing knowledge dissemination within the scientific community and beyond. The target audience for Free Science includes a diverse range of people, from researchers, academics, students, to the general public with an interest in science and academia. By promoting collaboration, open access principles, and introducing innovative funding models that minimize financial barriers for researchers and ensure fair compensation for reviewers, Free Science is poised to become a game-changer in the world of academic publishing. As the launch date for Free Science becomes near, anticipation is building for the arrival of this groundbreaking platform that promises to democratize access to scientific knowledge, drive collaboration, and elevate the standards of academic publishing. Stay tuned for more updates on this exciting venture that is set to redefine the landscape of scholarly communication.

Completing a PhD is a monumental achievement, a testament to years of hard work, resilience, and intellectual curiosity. But for many of us, the journey doesn’t end there. In fact, the transition from academia to “what comes next” can feel just as daunting—if not more so—than the PhD itself. The pressure to publish, the weight of being a “first author,” and the realization that universities and supervisors often prioritize papers over people can leave us feeling drained, questioning our worth, or even wondering, *What’s next?* If you’ve walked away from academia, you’re not alone. Many of us carry that mix of pride in what we’ve accomplished and an emptiness from realizing the system doesn’t always care about our growth or well-being. But here’s the good news: there’s something powerful about realizing we’re all navigating this together. It’s not about failure or success—it’s about taking back control of our lives and figuring out what truly matters to us. Reframing Success: Questions to consider. As we move forward, it’s worth reflecting on what success means to us now. Here are some questions to consider: How do you define success post-PhD? Is it about impact, balance, or something entirely different? Have you found a space—inside or outside academia—where you feel like you’re thriving? Is success enough, or are you also searching for significance—a deeper sense of purpose in what you do?** These questions aren’t easy to answer, but they’re essential for shaping a path that feels authentic and fulfilling. The Job Market Dilemma: Why We Feel Lost One of the biggest challenges PhDs face is the lack of preparation for the job market. Universities often focus on training us for academic careers, leaving many of us feeling ill-equipped to navigate non-academic roles. This disconnect can lead to feelings of being lost, undervalued, or unsure of how to translate our PhD into tangible opportunities. But here’s the thing: your PhD is more than just a research degree. It’s proof of your ability to solve complex problems, manage large projects, think critically, and communicate effectively. These are transferable skills that are highly valued in many industries—even if it doesn’t always feel that way. Changing the Narrative: It’s Not “Quitting,” It’s Choosing We need to change the narrative around “walking away” or “quitting” academia. The truth is, we’re not quitting—we’re simply finding a job after earning a degree, just like anyone else. A PhD is a qualification, not a life sentence. It’s okay to use it in ways that align with your values, passions, and well-being, even if that means leaving the traditional academic path. For many of us, leaving academia isn’t about giving up; it’s about choosing a path that feels right for us. It’s about recognizing that our PhD is a testament to our resilience and capability, but it doesn’t have to define our entire journey. You’re Not Alone: Building a Community The journey after a PhD can feel isolating, but it doesn’t have to be. There’s a growing community of PhDs who are redefining success, exploring new paths, and supporting each other along the way. Whether you’re staying in academia or venturing into uncharted territory, remember that you’re part of a larger network of people who understand your struggles and celebrate your wins. Final Thoughts Life after the PhD is about more than just finding a job—it’s about finding yourself. It’s about taking control of your narrative, embracing your strengths, and creating a life that aligns with your values and aspirations. So, to anyone feeling stuck or unsure about what comes next: You’re not alone. There’s something liberating about knowing we’re all figuring this out together, and it’s okay to take your time to find your way.

Simone Larivera The regulation of gene expression extends beyond transcription, with mRNA stability playing a crucial role in determining transcript lifespan and protein output. Degradation mechanisms safeguard cellular homeostasis, particularly in inflammatory responses where unchecked cytokine expression can lead to disease. A study by Bestehorn and colleagues expands the understanding of mRNA decay by demonstrating that tristetraprolin (TTP) licenses mRNA for degradation at the pre-mRNA stage, marking inflammatory transcripts for elimination before translation (Bestehorn et al., 2025). Nuclear Licensing of mRNA Decay TTP, also known as ZFP36, is an RNA-binding protein that directs cytokine mRNA degradation by recruiting the CCR4-NOT deadenylation complex and decapping enzymes (M. Fabian et al., 2013). This process ensures rapid clearance of inflammatory mediators such as Tnf, Il23, Il1a, or Ccl3 (Carballo et al., 2001, C. Molle et al., 2013, Kang et al., 2011, Sneezum et al., 2020). Traditionally, TTP has been thought to function in the cytoplasm, associating with mature mRNA to trigger degradation. However, Bestehorn and colleagues demonstrate that TTP primarily binds pre-mRNA in the nucleus, establishing a prerequisite step for subsequent decay. RNA Binding and Shuttling Are Essential for TTP-Mediated mRNA Regulation The nuclear binding of TTP is more than a mere preliminary pre-mRNA quality step, it is vital for the protein's overall regulatory function. Through proteomics and transcriptome- wide RNA-binding assays, the authors show that mutants of TTP, which fail to enter the nucleus, cannot recruit the necessary decay complexes, resulting in prolonged mRNA stability. This suggests that nuclear binding acts as a quality control checkpoint, ensuring that inflammatory transcripts are flagged for decay before they are exported. Notably, TTP's ability to shuttle between the nucleus and cytoplasm depends on its capacity to bind RNA, unlike most decay factors, which act on mRNAs already associated with ribosomes. Furthermore, blocking mRNA splicing causes TTP to accumulate in the nucleus, highlighting the complexity of the regulatory steps required for TTP's proper functioning. Thus, TTP's role in mRNA decay can be understood as a multi-step process: 1) TTP binds to pre-mRNA in the nucleus, specifically recognizing adenine-uridine-rich elements (AREs) within inflammatory transcripts. 2) Upon nuclear export, TTP remains attached to the mRNA, ensuring that the targeted transcripts are primed for degradation. 3) In the cytoplasm, TTP facilitates the recruitment of decay complexes, including CCR4-NOT and decapping enzymes, leading to efficient mRNA degradation. Evolutionary Conservation of Nuclear mRNA Licensing TTP's nuclear function is not unique to ZFP36. The authors extend their findings to ZFP36L1, a TTP paralog, suggesting that nuclear pre-mRNA binding is a conserved feature of this protein family. Both proteins require RNA binding for proper subcellular localization and function, with the RNA-binding-deficient mutants showing altered subcellular distributions and interactomes. The RNA-binding domain was shown to be critical for TTP’s involvement in RNA degradation pathways and cytoplasmic localization, reinforcing its role in regulating cytokine mRNA stability. Across species, TTP homologs share the capacity to interact with nuclear transcripts, reinforcing the idea that mRNA fate is determined early, before translation begins (Fu & Blackshear, 2017). Implications for Post-Transcriptional Control: Balancing mRNA stability and degradation The regulation of mRNA stability and decay is a critical process in controlling gene expression, especially during inflammatory responses. Two key RNA-binding proteins, TTP and HuR (ELAVL1), play central but opposing roles in this process. Both proteins bind to AU-rich elements (AREs) in target transcripts, but while TTP is best known for its role in mRNA destabilization, HuR acts as a stabilizing factor, binding as well, to ARE-containing transcripts and protecting them from degradation. One of HuR’s key functions is its ability to shield mRNAs from TTP-mediated decay, particularly in the nucleus. By binding to target transcripts in the nucleus, HuR can prevent TTP from accessing them, allowing select mRNAs to escape degradation and be exported to the cytoplasm (Herjan et al., 2014). This competition between TTP and HuR introduces a critical regulatory checkpoint, ensuring that cytokine production is both responsive and controlled. HuR’s role, however, extends beyond simple mRNA stabilization. Like, TTP, HuR shuttles between the nucleus and cytoplasm, a process regulated by a specific sequence in its hinge region (Fan et al., 1998). This shuttling allows HuR to bind target mRNAs in the nucleus and subsequently influence their stability and translation in the cytoplasm. Overexpression of HuR has been shown to enhance the stability of ARE-containing mRNAs, further highlighting its role as a counterbalance to TTP’s destabilizing function (Brennan & Steitz, 2001). Importantly, HuR’s binding is not limited to the 3′ UTR of mature mRNAs; it also interacts with intronic regions and poly-pyrimidine tracts in pre-mRNAs. Transcripts with binding sites in both intronic and 3′ UTR regions exhibit greater stabilization, suggesting that HuR couples pre-mRNA processing with mRNA stability. In this context, the findings of Bestehorn and colleagues suggest that TTP may also influence the fate of transcripts at earlier stages of RNA processing, adding a new dimension to its regulatory function. Together, TTP and HuR represent two sides of the same regulatory coin. TTP drives mRNA decay to limit inflammatory responses, while HuR stabilizes mRNAs to ensure timely and controlled cytokine production. These findings shift then the paradigm of mRNA degradation, establishing nuclear pre-mRNA binding as a key determinant of transcript fate. By licensing mRNA for degradation before cytoplasmic export, TTP provides an additional checkpoint in gene regulation, one that may extend beyond inflammation to other post-transcriptional regulators in cancer, neurodegeneration, and immune disorders. Future studies should explore where and how they might cooperate to regulate mRNA turnover, especially under specific cellular conditions that require a rapid inflammatory response.In conclusion, the study by Bestehorn et al. (2025) provides compelling evidence that nuclear pre-mRNA binding is not a passive event but an active decision point in gene expression. As the landscape of post-transcriptional regulation expands, understanding the interplay between nuclear and cytoplasmic mRNA processing will be essential in deciphering how cells fine-tune gene expression to maintain homeostasis and respond to environmental challenges. Citations: A. Bestehorn, J. von Wirén, C. Zeiler, J. Fesselet, S. Didusch, M. Forte, K. Doppelmayer, M. Borroni, A. Le Heron, S. Scinicariello,WeiQiang Chen, M. Baccarini ,V. Pfanzagl, Gijs A. Versteeg, M.Hartl, P. Kovarik Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision DOI: 10.1016/j.molcel.2025.01.001 Brennan CM, Steitz JA. HuR and mRNA stability. Cell Mol Life Sci. 2001 Feb;58(2):266- 77. doi: 10.1007/PL00000854. PMID: 11289308; PMCID: PMC11146503. Fabian MR, Frank F, Rouya C, Siddiqui N, Lai WS, Karetnikov A, Blackshear PJ, Nagar B, Sonenberg N. Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin. Nat Struct Mol Biol. 2013 Jun;20(6):735-9. doi: 10.1038/nsmb.2572. Epub 2013 May 5. PMID: 23644599; PMCID: PMC4811204. Carballo E, Cao H, Lai WS, Kennington EA, Campbell D, Blackshear PJ. Decreased sensitivity of tristetraprolin-deficient cells to p38 inhibitors suggests the involvement of tristetraprolin in the p38 signaling pathway. J Biol Chem. 2001 Nov 9;276(45):42580-7. doi: 10.1074/jbc.M104953200. Epub 2001 Sep 6. PMID: 11546803; PMCID: PMC1351389. Fan XC, Steitz JA. Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J. 1998 Jun 15;17(12):3448-60. doi: 10.1093/emboj/17.12.3448. PMID: 9628880; PMCID: PMC1170681. Fu M, Blackshear PJ. RNA-binding proteins in immune regulation: a focus on CCCH zinc finger proteins. Nat Rev Immunol. 2017 Feb;17(2):130-143. doi: 10.1038/nri.2016.129. Epub 2016 Dec 19. PMID: 27990022; PMCID: PMC5556700. Kang JG, Amar MJ, Remaley AT, Kwon J, Blackshear PJ, Wang PY, Hwang PM. Zinc finger protein tristetraprolin interacts with CCL3 mRNA and regulates tissue inflammation. J Immunol. 2011 Sep 1;187(5):2696-701. doi: 10.4049/jimmunol.1101149. Epub 2011 Jul 22. PMID: 21784977; PMCID: PMC3159726. Herjan T, Yao P, Qian W, Li X, Liu C, Bulek K, Sun D, Yang WP, Zhu J, He A, Carman JA, Erzurum SC, Lipshitz HD, Fox PL, Hamilton TA, Li X. HuR is required for IL-17-induced Act1-mediated CXCL1 and CXCL5 mRNA stabilization. J Immunol. 2013 Jul 15;191(2):640-9. doi: 10.4049/jimmunol.1203315. Epub 2013 Jun 14. PMID: 23772036; PMCID: PMC3722902. C. Molle, T. Zhang, L. Ysebrant de Lendonck, C. Gueydan, M. Andrianne, F.Sherer, G. Van Simaeys, P.J. Blackshear, O. Leo, S. Goriely Tristetraprolin regulation of interleukin 23 mRNA stability prevents a spontaneous inflammatory disease J. Exp. Med., 210 (2013), pp. 1675-1684, 10.1084/jem.20120707 Mukherjee N, Corcoran DL, Nusbaum JD, Reid DW, Georgiev S, Hafner M, Ascano M Jr, Tuschl T, Ohler U, Keene JD. Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell. 2011 Aug 5;43(3):327-39. doi: 10.1016/j.molcel.2011.06.007. Epub 2011 Jun 30. PMID: 21723170; PMCID: PMC3220597. Sneezum L, Eislmayr K, Dworak H, Sedlyarov V, Le Heron A, Ebner F, Fischer I, Iwakura Y, Kovarik P. Context-Dependent IL-1 mRNA-Destabilization by TTP Prevents Dysregulation of Immune Homeostasis Under Steady State Conditions. Front Immunol. 2020 Jul 7;11:1398. doi: 10.3389/fimmu.2020.01398. PMID: 32733464; PMCID: PMC7358311.

Free science means equal society In an increasingly interconnected world, disparities in access to knowledge and resources have become more and more evident. These inequalities manifest across various dimensions, including economic status, geographical location, and educational opportunities. The scientific community, while often seen as a source of progress and innovation, is not immune to these disparities. It is essential to recognize that equal justice in science is not only ideal; it is a necessity for creating a more equal society. This article explores the need for equal justice in science, emphasizing the importance of fair access to research, funding opportunities, and the peer review process. Supporting Students Globally Education is a powerful tool for change, yet many students, particularly in underrepresented regions, lack access to fellowships and financial support. By creating scholarship programs and funding opportunities for students from diverse backgrounds, we can empower the next generation of scientists and ensure that talent is not wasted due to financial constraints. This initiative not only embraces inclusivity but also enriches the scientific community with diverse perspectives and ideas. The Role of Workers in Science At the foundation of scientific research are the workers—scientists, researchers, and students who contribute their time and effort to advance knowledge. Unfortunately, many of these individuals face significant barriers, including lack of funding, inadequate institutional support, and limited access to publishing opportunities. To address these challenges, initiatives like Free Science aim to create a more inclusive environment for researchers worldwide. Peer Review and Its Importance The peer review process is a cornerstone of scientific integrity, ensuring that research is scrutinized and validated before publication. However, traditional models often overlook the contributions of reviewers, who play a critical role in maintaining quality standards. By implementing a system that compensates reviewers for their time and expertise, we can enhance the quality of research while promoting a more democratic and fair publishing environment. Collaboration and Public Engagement The primary audience for Free Science encompasses the scientific and academic community, alongside the broader public eager to engage with the latest research developments. What sets Free Science apart is its commitment to increase collaboration among researchers, enhancing public understanding and interest in science, and introducing a novel sponsorship model to alleviate financial burdens on researchers while compensating reviewers for their crucial contributions. Free Science: A New Paradigm for Open Access Free Science is not just another publishing platform; it is a meticulously designed open-access, peer-reviewed space where researchers can submit their manuscripts, undergo a rigorous peer review process, and ultimately have their findings shared with the world at no cost. The platform boasts an array of features, including: Easy submission system Streamlined peer review workflow Comprehensive editorial management tools Open-access repository DOI integration for easy referencing User account management Formatting and metadata support Community and discussion features to enhance collaboration Innovative Funding Avenues One of the most distinctive features of Free Science is the introduction of advertisements from external sources, a bold departure from the traditional academic publishing model. By making the platform open access to a global audience and exploring innovative funding avenues, Free Science is breaking new ground in the scholarly publishing landscape. This approach not only supports the financial sustainability of the platform but also ensures that research remains accessible to all, regardless of socioeconomic status. Conclusion: A Movement Towards Equitable Science While the exact launch date for Free Science remains to be determined, the anticipation and buzz surrounding this venture are palpable. As the platform prepares to dive into a new era of open-access publishing, one thing is clear: Free Science is not just a platform; it's a movement towards more accessible and collaborative scientific research dissemination. By addressing disparities in the scientific community and advocating for equal justice through science, we can pave the way for a future where knowledge is truly free and accessible to all.