@article{20728, abstract = {Glaciers are often located in steep mountain settings and avalanches from surrounding slopes can strongly influence snow accumulation patterns on their surface. This effect has however never been quantified for more than a few glaciers and the impact on the future evolution of glaciers is unclear. We coupled an avalanche and a glacier model to estimate the contribution of avalanches to the accumulation of all glaciers in the world and how this affects their evolution throughout the 21st century. Globally, 3% of the snow accumulation on glaciers comes from avalanches and 1% is removed by avalanches. This net contribution varies between regions and glaciers, with a maximum of 15% for New Zealand. Accounting for avalanches modifies the altitudinal pattern of glacier mass balance and the projected evolution of individual glaciers. The main effects include (1) a longer persistence of small glaciers, with for example three times more ice retained by glaciers smaller than 1 km2 in Central Europe under a low-emission scenario, and (2) an increased sensitivity of high-elevation accumulation zones to future warming. We anticipate the relative influence of avalanches to increase in the future and advocate for a better monitoring of this process and representation in glacier models.}, author = {Kneib, Marin and Maussion, Fabien and Brun, Fanny and Carcanade, Guillem and Farinotti, Daniel and Huss, Matthias and Van Tiel, Marit and Jouberton, Achille and Schmitt, Patrick and Schuster, Lilian and Dehecq, Amaury and Champollion, Nicolas}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Topographically-controlled contribution of avalanches to glacier mass balance in the 21st century}}, doi = {10.1038/s41467-025-65608-z}, volume = {16}, year = {2025}, } @inproceedings{20729, abstract = {Persistence modules (defined as a sequence of vector spaces and linear maps between them) are a key tool in topological data analysis. They are easy to interpret and fast to compute. However, when considering persistence maps (i.e. maps between persistence modules), these properties are lost. We propose a new invariant for persistence maps consisting of a partial matching such that: it is easy to interpret, it is more discriminative than the image of the persistence map, and can be calculated with cubical complexity.}, author = {Gonzalez-Diaz, Rocio and Soriano Trigueros, Manuel and Torras-Casas, Alvaro}, booktitle = {Proceedings of the 2025 International Symposium on Symbolic and Algebraic Computation}, isbn = {9798400720758}, location = {Guanajuato, Mexico}, pages = {188--196}, publisher = {Association for Computing Machinery}, title = {{Additive partial matchings for persistent homology}}, doi = {10.1145/3747199.3747561}, year = {2025}, } @article{20730, abstract = {Radio-frequency measurements could satisfy DiVincenzo’s readout criterion in future large-scale solid-state quantum processors, as they allow for high bandwidths and frequency multiplexing. However, the scalability potential of this readout technique can only be leveraged if quantum device tuning is performed using exclusively radio-frequency measurements, that is, without resorting to current measurements. We demonstrate an algorithm that performs automatic coarse tuning of double quantum dots with only radio-frequency measurements by exploiting their bandwidth and impedance matching. The tuning was completed within a few minutes with minimal prior knowledge about the device. Our results show that it is possible to eliminate the need for transport measurements for quantum-dot tuning, paving the way for more scalable device architectures.}, author = {Van Straaten, Barnaby and Fedele, Federico and Vigneau, Florian and Hickie, Joseph and Jirovec, Daniel and Ballabio, Andrea and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios and Ares, Natalia}, issn = {2331-7019}, journal = {Physical Review Applied}, number = {5}, publisher = {American Physical Society}, title = {{All-rf-based coarse-tuning algorithm for quantum devices using machine learning}}, doi = {10.1103/v11m-dbhm}, volume = {24}, year = {2025}, } @article{20731, abstract = {The adult human brain, under resting conditions, consumes approximately 20% of total body glucose, a demand that is even higher during the first decade of life. The brain metabolic landscape is intricately regulated throughout development, and each cell type exhibits distinct metabolic signatures at each specific stage. This picture becomes even more intricate when considering that metabolism is dynamically modulated to sustain critical biological processes, such as cell proliferation and differentiation and synaptic activity–dependent processes. The orchestration between metabolic regulation and the aforementioned physiological processes often relies on metabolism-dependent changes in the epigenetic landscape, which shape gene expression patterns to trigger selected downstream biological responses. Perturbations of brain metabolic pathways are frequently the cause of severe neurodevelopmental disorders. This review explores the latest insights into the regulation of brain metabolism in health and disease.}, author = {Marano, Domenico and Mariano, Vittoria and Novarino, Gaia}, issn = {1545-2948}, journal = {Annual Review of Genetics}, pages = {415--434}, publisher = {Annual Reviews}, title = {{Fueling the mind: Brain metabolism in health and neurodevelopmental disorders}}, doi = {10.1146/annurev-genet-111523-102424}, volume = {59}, year = {2025}, } @article{20732, abstract = {We investigate the real-time dynamics of a quenched quantum impurity immersed in a one-dimensional ultracold Fermi gas, focusing on the breakdown of the adiabatic Born-Oppenheimer approximation due to nonadiabatic effects. Despite a sizable impurity-bath mass imbalance, increasing interactions induce strong nonadiabatic couplings, disrupting adiabatic motion and enabling population transfer between the adiabatic potential energy curves. These transitions are governed by conical intersections arising from the pseudo Jahn-Teller effect, dynamically shaping the impurity's motion through the bath. Using ab initio simulations via the multilayer multiconfiguration time-dependent Hartree method and a multichannel Born-Oppenheimer framework, we track the impurity's evolution and directly prove the dynamical manifestation of the pseudo Jahn-Teller effect. We analyze two key scenarios: (i) a small initial shift, where a single avoided crossing drives transitions, and (ii) a large shift, where multiple avoided crossings lead to enhanced nonadiabaticity, self-trapping, and energy redistribution. Our findings establish ultracold fermionic few-body systems as tunable platforms for studying nonadiabatic quantum dynamics, opening new avenues for controlled impurity transport in strongly correlated environments.}, author = {Becker, A. and Koutentakis, Georgios and Schmelcher, P.}, issn = {2643-1564}, journal = {Physical Review Research}, number = {3}, publisher = {American Physical Society}, title = {{Dynamical probe of the pseudo Jahn-Teller effect in one-dimensional confined fermions}}, doi = {10.1103/2fr6-b59y}, volume = {7}, year = {2025}, } @article{20733, abstract = {The conversion of thermal energy into work is usually more efficient in the slow-driving regime, where the power output is vanishingly small. Efficient work extraction for fast-driving protocols remains an outstanding challenge at the nanoscale, where fluctuations play a significant role. In this Letter, we use a quantum-dot Szilard engine to extract work from thermal fluctuations with maximum efficiency over two decades of driving speed. We design and implement a family of optimized protocols ranging from the slow- to the fast-driving regime, and we measure the engine's efficiency as well as the mean and variance of its power output in each case. These optimized protocols exhibit significant improvements in power and efficiency compared to the naive approach. Our results also show that, when optimizing for efficiency, boosting the power output of a Szilard engine inevitably comes at the cost of increased power fluctuations.}, author = {Aggarwal, Kushagra and Rolandi, Alberto and Yang, Yikai and Hickie, Joseph and Jirovec, Daniel and Ballabio, Andrea and Chrastina, Daniel and Isella, Giovanni and Mitchison, Mark T. and Perarnau-Llobet, Martí and Ares, Natalia}, issn = {2643-1564}, journal = {Physical Review Research}, number = {3}, publisher = {American Physical Society}, title = {{Rapid optimal work extraction from a quantum-dot information engine}}, doi = {10.1103/q3dx-kyqj}, volume = {7}, year = {2025}, } @article{20734, abstract = {We consider the problem of parameter estimation in a high-dimensional generalized linear model. Spectral methods obtained via the principal eigenvector of a suitable data-dependent matrix provide a simple yet surprisingly effective solution. However, despite their wide use, a rigorous performance characterization, as well as a principled way to preprocess the data, are available only for unstructured (i.i.d. Gaussian and Haar orthogonal) designs. In contrast, real-world data matrices are highly structured and exhibit non-trivial correlations. To address the problem, we consider correlated Gaussian designs capturing the anisotropic nature of the features via a covariance matrix Σ. Our main result is a precise asymptotic characterization of the performance of spectral estimators. This allows us to identify the optimal preprocessing that minimizes the number of samples needed for parameter estimation. Surprisingly, such preprocessing is universal across a broad set of designs, which partly addresses a conjecture on optimal spectral estimators for rotationally invariant models. Our principled approach vastly improves upon previous heuristic methods, including for designs common in computational imaging and genetics. The proposed methodology, based on approximate message passing, is broadly applicable and opens the way to the precise characterization of spiked matrices and of the corresponding spectral methods in a variety of settings.}, author = {Zhang, Yihan and Ji, Hong Chang and Venkataramanan, Ramji and Mondelli, Marco}, issn = {2520-2324}, journal = {Mathematical Statistics and Learning}, number = {3-4}, pages = {193--304}, publisher = {EMS Press}, title = {{Spectral estimators for structured generalized linear models via approximate message passing}}, doi = {10.4171/MSL/52}, volume = {8}, year = {2025}, } @misc{20750, author = {Van Straaten, Barnaby and Fedele, Federico and Vigneau, Florian and Hickie, Joseph and Jirovec, Daniel and Chrastina, Daniel and Isella, Giovanni and Ares, Natalia}, publisher = {Zenodo}, title = {{All rf-based tuning algorithm for quantum devices using machine learning}}, doi = {10.5281/ZENODO.17352653}, year = {2025}, } @article{20767, abstract = {Chemistry education at the graduate level and beyond faces the formidable challenge of a boundless and constantly expanding frontier of knowledge on many fronts. While modern learners have an increasingly broad range of resources available at their disposal (including open access text-based references, online videos, training problems, and other digital learning materials), there are comparatively fewer such materials aimed at the highest levels of study. With the goal of producing widely accessible graduate-level learning content, we created a community-based approach to online course design that is easily digestible to meet the expectations of modern learners. Herein, we report the development of an open access Advanced Organic Chemistry video-based online course and several other specialized minicourses using the Synthesis Workshop YouTube channel.}, author = {Horwitz, Matthew A. and Al-Ahmad, Reem and Bai, Xingfeng and Balletti, Matteo and Bellotti, Peter and Ben-Tal, Yael and Campbell, Mark W. and Cheasty, Kathleen and Crossley, Steven W. M. and Day, Craig S. and Deneny, Patrick J. and Forbes, Katherine C. and Gogarnoiu, Emma S. and Grant, Phillip S. and Halder, Riya and Harris, Georgia R. and Hernández-Lladó, Pol and Jouanneau, Morgan and Jost, Vera and Kutateladze, Dennis A. and Laudadio, Gabriele and Liu, Chun and Looby, Aidan P. and Maestro, Aitor and McCallum, Terry and Palkowitz, Maximilian D. and Paolillo, Joshua M. and Perry, Matthew W. D. and Reisenbauer, Julia and Reyes, Cesar and Sharma, Hayden A. and Sheong, Fu Kit and Thoma, Benjamin and Tran, Andrew V. and Tran, Duc N. and Aguilar Troyano, Francisco José and Verheyen, Thomas and Walsh, Mark P. and Wagner, Alicia and Wearing, Emily R. and Wuitschik, Georg}, issn = {1938-1328}, journal = {Journal of Chemical Education}, number = {9}, pages = {3777--3783}, publisher = {American Chemical Society}, title = {{Reimagining advanced chemistry education: A community-based approach to course design for modern learners}}, doi = {10.1021/acs.jchemed.5c00555}, volume = {102}, year = {2025}, } @article{20796, abstract = {Rapid prophase chromosome movements ensure faithful alignment of the parental homologous chromosomes and successful synapsis formation during meiosis. These movements are driven by cytoplasmic forces transmitted to the nuclear periphery, where chromosome ends are attached through transmembrane proteins. During many developmental stages a specific genome architecture with chromatin nuclear periphery contacts mediates specific gene expression. Whether chromatin is removed from the nuclear periphery as a consequence of chromosome motions or by a specific mechanism is not fully understood. Here, we identify a mechanism to remove chromatin from the nuclear periphery through vaccinia related kinase (VRK-1)–dependent phosphorylation of Barrier to Autointegration Factor 1 (BAF-1) in Caenorhabditis elegans early prophase of meiosis. Interfering with chromatin removal delays chromosome pairing, impairs synapsis, produces oocytes with abnormal chromosomes and elevated apoptosis. Long read sequencing reveals deletions and duplications in offspring lacking VRK-1 underscoring the importance of the BAF-1–VRK-1 module in preserving genome stability in gametes during rapid chromosome movements.}, author = {Paouneskou, Dimitra and Baudrimont, Antoine and Kelemen, Réka K and Elkrewi, Marwan N and Graf, Angela and Moukbel Ali Aldawla, Shehab and Kölbl, Claudia and Tiemann-Boege, Irene and Vicoso, Beatriz and Jantsch, Verena}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{BAF-1–VRK-1 mediated release of meiotic chromosomes from the nuclear periphery is important for genome integrity}}, doi = {10.1038/s41467-025-65420-9}, volume = {16}, year = {2025}, } @article{20797, abstract = {Quantum key distribution (QKD) offers a theoretically secure method to share secret keys, yet practical implementations face challenges due to noise and loss over long-distance channels. Traditional QKD protocols require extensive noise compensation, hindering their industrial scalability and lowering the achievable key rates. Alternative protocols encode logical qubits in noise-resilient states but at the cost of using many physical qubits, increasing susceptibility to loss and limiting transmission distance. In this work, we introduce a logical-qubit encoding that uses antisymmetric Bell states in the continuous photonic degrees of freedom, frequency and time. By leveraging the continuous space, we overcome this noise-loss robustness trade-off by minimizing the number of photons per logical qubit while optimizing the encoding resilience over noise fluctuations. We analyze the security of our encoding and demonstrate its robustness compared to existing state-of-the-art protocols. This approach provides a path toward scalable, efficient QKD implementations under realistic noise conditions.}, author = {Seabrook, Hannah and Lavie, Emilien and Strömberg, Karl T and Stafford, Matthew P. and Rubino, Giulia}, issn = {2331-7019}, journal = {Physical Review Applied}, number = {2}, publisher = {American Physical Society}, title = {{Surpassing the loss-noise robustness trade-off in quantum key distribution}}, doi = {10.1103/xq2l-r4r7}, volume = {24}, year = {2025}, } @unpublished{20804, abstract = {RNA polymerase II (Pol II) must be assembled in the cytoplasm before it enters the nucleus, where it transcribes protein-coding genes. Although transcription by Pol II is intensively studied, how this central multi-subunit enzyme is made and the role of dedicated factors remains unclear. Here, we report the integrative structural analysis of a native human Pol II from the cytoplasm captured near the end of biogenesis. The complex contained Gdown1 and three biogenesis factors – RPAP2 and the critical small GTPases GPN1 and GPN3. Cryo-EM analysis of the complex revealed how Gdown1 and RPAP2 associate with Pol II and prevent the premature association of transcription factors. Further biochemical and cryo-EM analysis revealed how RPAP2 recruits GPN1–GPN3 to the complex, and how the assembly of the RPAP2–GPN1–GPN3 complex is controlled by GTP hydrolysis. The combined results uncover a network of interactions that chaperone cytoplasmic Pol II to prevent aberrant interactions, reveal a GTP-controlled switch during the final stages of Pol II biogenesis, and suggest a general mechanism for the action of GPN-loop GTPase family of enzymes.}, author = {Hlavata, Annamaria and Neuditschko, Benjamin and Schellhaas, Ulla and Plaschka, Clemens and Herzog, Franz and Bernecky, Carrie A}, publisher = {bioRxiv}, title = {{Structure of cytoplasmic RNA polymerase II}}, doi = {10.64898/2025.12.10.692585}, year = {2025}, } @article{20814, abstract = {We characterize all semigroups sandwiched between the semigroup of a Dirichlet form and the semigroup of its active main part. In case the Dirichlet form is regular, we give a more explicit description of the quadratic forms of the sandwiched semigroups in terms of pairs consisting of an open set and a measure on an abstract boundary.}, author = {Keller, Matthias and Lenz, Daniel and Schmidt, Marcel and Schwarz, Michael and Wirth, Melchior}, issn = {1572-929X}, journal = {Potential Analysis}, publisher = {Springer Nature}, title = {{Boundary representations of intermediate forms between a regular Dirichlet form and its active main part}}, doi = {10.1007/s11118-025-10251-y}, volume = {64}, year = {2025}, } @article{20816, abstract = {Background: DNA methylation (DNAm) can regulate gene expression, and its genome-wide patterns (epigenetic scores or EpiScores) can act as biomarkers for complex traits. The relative stability of methylation profiles may enable better assessment of chronic exposures compared to single time-point protein measures. We present the first large-scale epigenetic study of the highly-abundant serum proteome measured via ultra-high throughput mass spectrometry in 14,671 samples from the Generation Scotland cohort. We further demonstrate the first large-scale comparison of protein EpiScores and their respective proteins as predictors of incident cardiovascular disease. Results: Marginal epigenome-wide association models, adjusting for age, sex, measurement batch, estimated white cell proportions, BMI, smoking and methylation principal components, reveal 15,855 significant CpG – protein associations across 125 of 133 proteins PBonferroni < 2.71 × 10-10. Bayesian epigenome-wide association studies of the same 133 proteins reveal 697 CpG-Protein associations (posterior inclusion probability > 0.95). 112 protein EpiScores correlate significantly with their respective protein in a holdout test-set. Of these, sixteen associate significantly with incident all-cause cardiovascular disease (Nevents=191) compared to one measured protein. Conclusions: We highlight a complex interplay between the blood-based methylome and proteome. Importantly, we show that protein EpiScores correlate with measured proteins and demonstrate that the, as-yet understudied, high-abundance proteome may yield clinically relevant biomarkers. The protein EpiScores demonstrate more significant associations with cardiovascular disease than directly measured proteins, suggesting their potential as clinical biomarkers for monitoring or predicting disease risk. We suggest that biomarker development could be enhanced by the consideration of protein EpiScores alongside measured proteins.}, author = {Robertson, Josephine A. and Bajzik, Jakub and Vernardis, Spyros and Chybowska, Aleksandra D. and Mccartney, Daniel L. and Grauslys, Arturas and Mur, Jure and Smith, Hannah M. and Campbell, Archie and Drake, Camilla and Grant, Hannah and Pearce, Jamie and Russ, Tom C. and Adkin, Poppy and White, Matthew and Brigden, Charles and Messner, Christoph B. and Porteous, David J. and Hayward, Caroline and Cox, Simon R. and Zelezniak, Aleksej and Ralser, Markus and Robinson, Matthew Richard and Marioni, Riccardo E.}, issn = {1474-760X}, journal = {Genome Biology}, publisher = {Springer Nature}, title = {{Methylome-wide association studies and epigenetic biomarker development for 133 mass spectrometry-assessed circulating proteins in 14,671 Generation Scotland participants}}, doi = {10.1186/s13059-025-03892-0}, volume = {26}, year = {2025}, } @inproceedings{20817, abstract = {We present Mechanistic PDE Networks -- a model for discovery of governing partial differential equations from data. Mechanistic PDE Networks represent spatiotemporal data as space-time dependent linear partial differential equations in neural network hidden representations. The represented PDEs are then solved and decoded for specific tasks. The learned PDE representations naturally express the spatiotemporal dynamics in data in neural network hidden space, enabling increased modeling power. Solving the PDE representations in a compute and memory-efficient way, however, is a significant challenge. We develop a native, GPU-capable, parallel, sparse and differentiable multigrid solver specialized for linear partial differential equations that acts as a module in Mechanistic PDE Networks. Leveraging the PDE solver we propose a discovery architecture that can discovers nonlinear PDEs in complex settings, while being robust to noise. We validate PDE discovery on a number of PDEs including reaction-diffusion and Navier-Stokes equations.}, author = {Pervez, Adeel A and Gavves, Efstratios and Locatello, Francesco}, booktitle = {42nd International Conference on Machine Learning}, issn = {2640-3498}, location = {Vancouver, Canada}, pages = {48962--48973}, publisher = {ML Research Press}, title = {{Mechanistic PDE networks for discovery of governing equations}}, volume = {267}, year = {2025}, } @article{20818, abstract = {This study demonstrates that Marchantia non-canonical PINs are predominantly localized to the plasma membrane, with MpPINX and MpPINW exhibiting asymmetric distribution. A newly identified miniW domain within the MpPINW hydrophilic loop governs subcellular trafficking and asymmetric PM localization of non-canonical PINs in Marchantia.}, author = {Tang, Han and Smoljan, Adrijana and Zou, Minxia and Zhang, Yuzhou and Lu, Kuan Ju and Friml, Jiří}, issn = {1365-3040}, journal = {Plant Cell and Environment}, publisher = {Wiley}, title = {{The miniW domain directs polarized membrane localization of non-canonical PINs in Marchantia polymorpha}}, doi = {10.1111/pce.70295}, year = {2025}, } @article{18753, abstract = {We continue a line of research which studies which hereditary families of digraphs have bounded dichromatic number. For a class of digraphs C, a hero in C is any digraph H such that H -free digraphs in C have bounded dichromatic number. We show that if F is an oriented star of degree at least five, the only heroes for the class of F -free digraphs are transitive tournaments. For oriented stars F of degree exactly four, we show the only heroes in F -free digraphs are transitive tournaments, or possibly special joins of transitive tournaments. Aboulker et al. characterized the set of heroes of {H,K1+P2→} -free digraphs almost completely, and we show the same characterization for the class of {H,rK1+P3→} -free digraphs. Lastly, we show that if we forbid two "valid" orientations of brooms, then every transitive tournament is a hero for this class of digraphs.}, author = {Carbonero, Alvaro and Koerts, Hidde and Moore, Benjamin and Spirkl, Sophie}, issn = {0195-6698}, journal = {European Journal of Combinatorics}, publisher = {Elsevier}, title = {{On heroes in digraphs with forbidden induced forests}}, doi = {10.1016/j.ejc.2024.104104}, volume = {125}, year = {2025}, } @article{18754, abstract = {Exploring the molecular correlates of metabolic health measures may identify their shared and unique biological processes and pathways. Molecular proxies of these traits may also provide a more objective approach to their measurement. Here, DNA methylation (DNAm) data were used in epigenome-wide association studies (EWASs) and for training epigenetic scores (EpiScores) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio, and blood-based measures of glucose, high-density lipoprotein cholesterol, and total cholesterol in >17,000 volunteers from the Generation Scotland (GS) cohort. We observed a maximum of 12,033 significant findings (p < 3.6 × 10−8) for BMI in a marginal linear regression EWAS. By contrast, a joint and conditional Bayesian penalized regression approach yielded 27 high-confidence associations with BMI. EpiScores trained in GS performed well in both Scottish and Singaporean test cohorts (Lothian Birth Cohort 1936 [LBC1936] and Health for Life in Singapore [HELIOS]). The EpiScores for BMI and total cholesterol performed best in HELIOS, explaining 20.8% and 7.1% of the variance in the measured traits, respectively. The corresponding results in LBC1936 were 14.4% and 3.2%, respectively. Differences were observed in HELIOS for body fat, where the EpiScore explained ∼9% of the variance in Chinese and Malay -subgroups but ∼3% in the Indian subgroup. The EpiScores also correlated with cognitive function in LBC1936 (standardized βrange: 0.08–0.12, false discovery rate p [pFDR] < 0.05). Accounting for the correlation structure across the methylome can vastly affect the number of lead findings in EWASs. The EpiScores of metabolic traits are broadly applicable across populations and can reflect differences in cognition.}, author = {Smith, Hannah M. and Ng, Hong Kiat and Moodie, Joanna E. and Gadd, Danni A. and Mccartney, Daniel L. and Bernabeu, Elena and Campbell, Archie and Redmond, Paul and Taylor, Adele and Page, Danielle and Corley, Janie and Harris, Sarah E. and Tay, Darwin and Deary, Ian J. and Evans, Kathryn L. and Robinson, Matthew Richard and Chambers, John C. and Loh, Marie and Cox, Simon R. and Marioni, Riccardo E. and Hillary, Robert F.}, issn = {1537-6605}, journal = {American Journal of Human Genetics}, number = {1}, pages = {106--115}, publisher = {Elsevier}, title = {{DNA methylation-based predictors of metabolic traits in Scottish and Singaporean cohorts}}, doi = {10.1016/j.ajhg.2024.11.012}, volume = {112}, year = {2025}, } @inbook{18765, abstract = {Mosaic Analysis with Double Markers (MADM) represents a mouse genetic approach coupling differential fluorescent labeling to genetic manipulations in dividing cells and their lineages. MADM uniquely enables the generation and visualization of individual control or homozygous mutant cells in a heterozygous genetic environment. Among its diverse applications, MADM has been used to dissect cell-autonomous gene functions important for cortical development and neural development in general. The high cellular resolution offered by MADM also permits the analysis of transcriptomic changes of individual cells upon genetic manipulations. In this chapter, we describe an experimental protocol combining the generation and isolation of MADM-labeled cells with downstream single-cell RNA-sequencing technologies to probe cell-type specific phenotypes due to genetic mutations at single-cell resolution.}, author = {Cheung, Giselle T and Pauler, Florian and Hippenmeyer, Simon}, booktitle = {Lineage Tracing}, editor = {Garcia-Marques, Jorge and Lee, Tzumin}, isbn = {9781071643099}, issn = {1940-6029}, pages = {139--151}, publisher = {Springer Nature}, title = {{Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM)}}, doi = {10.1007/978-1-0716-4310-5_7}, volume = {2886}, year = {2025}, } @article{18778, abstract = {Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryogenic-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation. Further, we show how distinct domains of the general transcription factor TFIIF control repressive activity. Together, we reveal how a noncoding RNA can regulate mammalian gene expression.}, author = {Tluckova, Katarina and Kaczmarek, Beata M and Testa Salmazo, Anita P and Bernecky, Carrie A}, issn = {1545-9985}, journal = {Nature Structural & Molecular Biology}, pages = {607--612}, publisher = {Springer Nature}, title = {{Mechanism of mammalian transcriptional repression by noncoding RNA}}, doi = {10.1038/s41594-024-01448-7}, volume = {32}, year = {2025}, }