Wihuri Research Institute

Silencing of researchers refers to informal or formal actions that restrict what scientists can study, say, publish, or teach. Reasons for silencing can be related to political, economic, or ideological interests. It is widely recognized as a threat to academic freedom and to the public’s access to independent knowledge.Internationally, climate change research has been one of the topics most often targeted with silencing attempts. In the Finnish context, one branch of the polarized climate change discussion has revolved around forest management and use. In 2024, the national broadcasting company Yle brought up a story about silencing attempts of both individual researchers and academic institutions by forestry companies and their lobbying organizations but also by policymakers.The equality and work wellbeing group at the Institute of Atmospheric and Earth System Research (INAR) of the University of Helsinki, Finland, wanted to find out how much our researchers have faced silencing attempts or exterior pressure, how it has affected them, and how they have reacted. We designed a short survey that was sent to all staff members.We received a total of 55 answers (about 20% of the staff members). 13 respondents had personal experiences of pressure or silencing. In the majority of these experiences, the attempted suppressing came from within the academia, although a few reported silencing attempts also came from the public administration, private sector, and social media.Reactions of the respondents who had experienced silencing or pressure varied from self-censorship and giving in to the pressure to having a dialogue with the source of the pressure. Discussions with peers were considered important.In the survey, we also asked the respondents to suggest actions to make our work and research community stronger against such pressures. Three kinds of actions were suggested. First, education on the topic, focusing especially on early-career scientists and non-Finnish speakers. Second, provision of resources and tools for individual researchers, for example a guide for identifying this kind of pressure, common guidelines for responding to silencing attempts, as well as easy and anonymous channels for reporting. Third, introducing institutional policies and enhancing scientific culture, for example strengthening mentorship practices and peer support, and more ambitious promotion of open and honest science.We presented the results of the survey in our institute’s weekly seminar. We had also three experts of experience sharing their stories, discussions in small groups, and an external expert’s note by a representative of the national committee for public information.In conclusion, carrying out this survey was helpful for getting an idea of what kinds of silencing attempts our researchers experience and how common it is. It is clear that the consequences of this are serious for both the individual targeted scientists and the integrity of science. We need to respond as a research community, and we now have good ideas about how to do that.

The growing demand for sustainable aviation fuels (SAFs) has driven interest in biomass-derived fuel precursors. This study investigates the aldol condensation of furfural and cyclopentanone (CP) over a series of Ce-modified zeolites and mesoporous catalysts to produce 2-(2-furylmethylidene) CP (FC) and its dimer 2,5-bis(2-furylmethylidene) CP (F2C), both relevant as SAF intermediates. A range of Ce-based materials, including Ce–H–Y-80, Ce-MCM-41, Ce-SBA-15, and Ce–H-Beta with varying Si/Al ratios, were synthesized and tested under specific reaction conditions. Catalyst characterization revealed distinct differences in surface area, acidity, basicity, and pore architecture, all contributing to the performance. Ce-MCM-41 exhibited the highest selectivity to FC (57%) at 65% conversion, linked to its mesoporosity and balanced acid–base properties. To further assess this catalyst’s performance, additional kinetic studies and reaction modeling were conducted, along with extended characterization of the spent and regenerated catalyst to evaluate stability and reusability. Zeolitic Ce–H–Beta catalysts demonstrated strong Brønsted acidity and delivered high conversion with moderate selectivity. A mechanistic correlation between acidity/basicity and activity was supported by the literature data. These findings highlight the potential of Ce-based heterogeneous catalysts in upgrading biomass-derived compounds into SAF precursors and support further development of regenerable, multifunctional catalytic materials.

To systematically identify causal genetic mechanisms that confer risk for coronary artery disease (CAD) in GWAS loci, we mapped genome-wide variant-to-enhancer-to-gene (V2E2G) links in vascular smooth muscle cells (SMC). Enhancers identified by active chromatin features, and further prioritized by base-resolution deep learning models of chromatin accessibility in 108 CAD loci, were studied with CRISPRi targeting and Direct-Capture Targeted Perturb-seq (DC-TAP-seq) evaluation of 470 genes. Seventy-six V2E2G links were identified for 59 candidate CAD genes representing gene programs including epithelial-mesenchymal transformation, ubiquitination, and protein folding as well as BMP and TGFB signaling. Similar methods employed with an independent focused screen targeting one candidate locus at 9p21.3 identified 10 enhancers regulating expression of multiple genes at this location. Detailed molecular studies revealed that two enhancers mediating transcription factor binding and transcriptional regulation contribute to ancestry-specific and sex-specific risk for CAD and the surrogate biomarker vascular calcification. Together, these studies advance our identification of GWAS CAD V2E2G links across the genome, and specific mechanisms of risk at the complex 9p21.3 locus.

The meninges, consisting of the dura, arachnoid and pia mater that surround the brain and spinal cord, have been recognized from the earliest anatomical studies. First identified in 1787, lymphatic vessels in the dura are now receiving greater attention as their contribution to cerebrospinal fluid (CSF) clearance in diverse neurological conditions is being investigated. New methods have increased the understanding of dural lymphatics, but much is still being learned about their heterogeneity, intracranial and extracranial connections, and factors that govern their functions and maintenance. Current research is striving to understand the regulation of CSF drainage and influence of brain antigen and immune cell transit through dural lymphatics on aging impairments and the severity of neurodegenerative and neuroimmune diseases, traumatic brain injury, stroke and other neurological disorders. Achieving these goals should lead to safe and effective methods for manipulating CSF clearance through dural lymphatics for therapeutic benefit.

AimsMembers of the VEGF family are crucial modulators of vascular and neural function. While VEGFA signalling has been shown to mitigate several aging-related cardiac phenotypes and prolong survival in aged mice, the role of VEGFB in cardiac aging remains underexplored. In this study, we identify a significant decline in Vegfb expression, particularly of its soluble isoform Vegfb186, in aged mouse and human hearts. To assess the therapeutic potential of VEGFB in aging-associated cardiac pathologies, we used AAV9-mediated gene transfer to overexpress Vegfb186 in 18-month-old male C57Bl/6J mice.Methods and resultsVEGFB is known to exhibit vascular and neuroprotective effects that we assessed in the ageing heart. In the aged heart, doses of Vegfb186 overexpression that had only a modest effect on the vascular endothelium prevented age-induced diastolic dysfunction and fibrosis. Vegfb186 treatment additionally restored sympathetic and sensory nerve fibre density and increased heart rate variability. Although Vegfb186 overexpression induced cardiac hypertrophy, our findings indicated that this hypertrophy was compensatory rather than pathological as Vegfb186 overexpression corrected the elevated cardiomyocyte length-to-width ratio observed in aged hearts, a metric typically indicative of pathological remodelling. Cardiac single-nucleus RNA sequencing of the hearts and in vitro analysis of the cardiomyocytes indicated up-regulation of the STAT3 signal transduction pathway as a potential contributor of VEGFB-induced cardiac hypertrophy.ConclusionOur findings demonstrate that Vegfb186 overexpression partially reverses age-related cardiac pathologies such as diastolic dysfunction and fibrosis. This work highlights VEGFB as a potential therapeutic target for combating cardiac aging and its associated dysfunctions.

Cell fate plasticity enables development, yet unlocked plasticity is a cancer hallmark. While transcription master regulators induce lineage-specific genes to restrict plasticity, it remains unclear whether plasticity is actively suppressed by lineage-specific repressors. Here we computationally predict so-called safeguard repressors for 18 cell types that block phenotypic plasticity lifelong. We validated hepatocyte-specific candidates using reprogramming, revealing that prospero homeobox protein 1 (PROX1) enhanced hepatocyte identity by direct repression of alternative fate master regulators. In mice, Prox1 was required for efficient hepatocyte regeneration after injury and was sufficient to prevent liver tumorigenesis. In line with patient data, Prox1 depletion caused hepatocyte fate loss in vivo and enabled the transition of hepatocellular carcinoma to cholangiocarcinoma. Conversely, overexpression promoted cholangiocarcinoma to hepatocellular carcinoma transdifferentiation. Our findings provide evidence for PROX1 as a hepatocyte-specific safeguard and support a model where cell-type-specific repressors actively suppress plasticity throughout life to safeguard lineage identity and thus prevent disease.

The vasculature, present in all tissues, has long been regarded as a mere conduit for oxygen, nutrients, and waste. However, recent research has unveiled endothelial cells as dynamic regulators of tissue homeostasis, capable of influencing organ growth and regeneration through secreted factors called angiocrines [1-4]. The discovery of angiocrines as key mediators of endothelial-parenchymal interactions is transforming our understanding of regenerative medicine and targeted therapies. Follert et al. hypothesize that flow-responsive angiocrines act as central orchestrators of tissue regrowth and regeneration, triggered by mechanical stimuli on endothelial cells following partial organ resection [5]. The currently known liver, lung, and kidney angiocrines are presented with special focus on the recently identified myeloid-derived growth factor (MYDGF) and hepatocyte growth factor (HGF). Different tissues have very different abilities to regenerate after injury or surgical resection. In both mice and humans, the liver exhibits remarkable regenerative capacity, capable of restoring its mass within weeks after losing more than half of its volume, whereas, for example the heart has a very poor regeneration capacity. Compared to the liver, the kidney and lung show limited and delayed compensatory growth, highlighting a spectrum of regenerative potential across organs. Elegant previous experiments have demonstrated that liver regrowth is dependent on angiogenic response and the production of angiocrines, highlighting the crucial role of endothelial cells in the liver growth and regeneration process [6, 7]. To date, several different proteins have been identified as angiocrines produced by the liver endothelial cells with growth-promoting effects. Less is known about angiocrines regulating growth and regeneration in the kidney and lung. Thus, understanding the organ-specific angiocrine signaling during tissue growth, homeostasis, and disease is a key for the development of new therapeutic approaches to maintain organ health and initiate organ renewal. Endothelial cells experience laminar shear stress induced by blood flow, which is presicely adjusted to the physiological needs of each organ. Investigating how flow-responsive angiocrines vary between physiological stresses, such as exercise, and pathological conditions (organ resection or trauma), could unveil distinct regenerative mechanisms. Blood flow, blood pressure, and the amount of mechanical stretching to endothelial cells can rapidly change, for example, in response to acute trauma or heavy exercise. Severe changes in blood flow also occur after partial organ resection, which is the main topic of this hypothesis [5]. The hypothesis also touches upon the pivotal role of angiocrines in tumor progression, suggesting that angiocrines regulate cancer cell behavior and metastasis. Vascular morphology and function are very different in solid tumors compared to healthy tissues, affecting blood flow patterns and mechanoelastic stretch in endothelial cells. Several angiocrines have been shown to influence tumor cell dynamics, but future research should focus on identifying tumor type-specific angiocrines to inform targeted therapies. Understanding tumor-specific angiocrines and their interplay with the tumor microenvironment could pave the way for targeted therapies to inhibit tumor progression Our understanding of endothelial cells and their angiocrine secretome in regulating organ-specific development, maintenance, and regeneration is fast expanding, with vast potential for therapeutic exploration. It is important to note that, in addition to proteins, metabolites or small molecules are also produced and released by endothelial cells. These different types of angiocrines can function locally on adjacent cells or travel through the bloodstream to distant organs, underscoring the complexity and versatility of angiocrine signaling. Future studies will leverage novel single-cell techniques to decode angiocrine diversity across organotypic niches and health states, offering precision interventions for different diseases. This article comments on the hypothesis paper by Paula Follert, Linda Große-Segerath, and Eckhard Lammert, https://doi.org/10.1002/bies.202400207