@article{18757, abstract = {Segmentation is a critical data processing step in many applications of cryo-electron tomography. Downstream analyses, such as subtomogram averaging, are often based on segmentation results, and are thus critically dependent on the availability of open-source software for accurate as well as high-throughput tomogram segmentation. There is a need for more user-friendly, flexible, and comprehensive segmentation software that offers an insightful overview of all steps involved in preparing automated segmentations. Here, we present Ais: a dedicated tomogram segmentation package that is geared towards both high performance and accessibility, available on GitHub. In this report, we demonstrate two common processing steps that can be greatly accelerated with Ais: particle picking for subtomogram averaging, and generating many-feature segmentations of cellular architecture based on in situ tomography data. Featuring comprehensive annotation, segmentation, and rendering functionality, as well as an open repository for trained models at aiscryoet.org, we hope that Ais will help accelerate research and dissemination of data involving cryoET.}, author = {Last, Mart G.F. and Abendstein, Leoni and Voortman, Lenard M. and Sharp, Thomas H.}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Streamlining segmentation of cryo-electron tomography datasets with Ais}}, doi = {10.7554/eLife.98552}, volume = {13}, year = {2024}, } @article{18445, abstract = {Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1+/Onecut1/2+ proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH)+ glutamate neurons through neuron navigator-2 (NAV2). In vivo, siRNA-mediated knockdown of ONECUT3 in neonatal mice reduced NAV2 mRNA, as well as neurite complexity in Onecut3-containing neurons, while genetic deletion of Onecut3/ceh-48 in C. elegans impaired neurocircuit wiring, and sensory discrimination-based behaviors. Thus, ONECUT3, conserved across neuronal subtypes and many species, underpins the polarization and morphological plasticity of phenotypically distinct neurons that descend from a common pool of Ascl1+ progenitors in the hypothalamus.}, author = {Zupančič, Maja and Keimpema, Erik and Tretiakov, Evgenii O. and Eder, Stephanie J. and Lev, Itamar and Englmaier, Lukas and Bhandari, Pradeep and Fietz, Simone A. and Härtig, Wolfgang and Renaux, Estelle and Villunger, Andreas and Hökfelt, Tomas and Zimmer, Manuel and Clotman, Frédéric and Harkany, Tibor}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3}}, doi = {10.1038/s41467-024-52762-z}, volume = {15}, year = {2024}, } @inproceedings{14213, abstract = {We introduce a method to segment the visual field into independently moving regions, trained with no ground truth or supervision. It consists of an adversarial conditional encoder-decoder architecture based on Slot Attention, modified to use the image as context to decode optical flow without attempting to reconstruct the image itself. In the resulting multi-modal representation, one modality (flow) feeds the encoder to produce separate latent codes (slots), whereas the other modality (image) conditions the decoder to generate the first (flow) from the slots. This design frees the representation from having to encode complex nuisance variability in the image due to, for instance, illumination and reflectance properties of the scene. Since customary autoencoding based on minimizing the reconstruction error does not preclude the entire flow from being encoded into a single slot, we modify the loss to an adversarial criterion based on Contextual Information Separation. The resulting min-max optimization fosters the separation of objects and their assignment to different attention slots, leading to Divided Attention, or DivA. DivA outperforms recent unsupervised multi-object motion segmentation methods while tripling run-time speed up to 104FPS and reducing the performance gap from supervised methods to 12% or less. DivA can handle different numbers of objects and different image sizes at training and test time, is invariant to permutation of object labels, and does not require explicit regularization.}, author = {Lao, Dong and Hu, Zhengyang and Locatello, Francesco and Yang, Yanchao and Soatto, Stefano}, booktitle = {1st Conference on Parsimony and Learning}, location = {Hong Kong, China}, title = {{Divided attention: Unsupervised multi-object discovery with contextually separated slots}}, year = {2024}, } @inproceedings{18114, abstract = {This paper presents Mechanistic Neural Networks, a neural network design for machine learning applications in the sciences. It incorporates a new Mechanistic Block in standard architectures to explicitly learn governing differential equations as representations, revealing the underlying dynamics of data and enhancing interpretability and efficiency in data modeling. Central to our approach is a novel Relaxed Linear Programming Solver (NeuRLP) inspired by a technique that reduces solving linear ODEs to solving linear programs. This integrates well with neural networks and surpasses the limitations of traditional ODE solvers enabling scalable GPU parallel processing. Overall, Mechanistic Neural Networks demonstrate their versatility for scientific machine learning applications, adeptly managing tasks from equation discovery to dynamic systems modeling. We prove their comprehensive capabilities in analyzing and interpreting complex scientific data across various applications, showing significant performance against specialized state-of-the-art methods. Source code is available at https://github.com/alpz/mech-nn.}, author = {Pervez, Adeel A and Locatello, Francesco and Gavves, Efstratios}, booktitle = {Proceedings of the 41st International Conference on Machine Learning}, issn = {2640-3498}, location = {Vienna, Austria}, pages = {40484--40501}, publisher = {ML Research Press}, title = {{Mechanistic neural networks for scientific machine learning}}, volume = {235}, year = {2024}, } @inproceedings{18964, abstract = {Object-centric learning (OCL) extracts the representation of objects with slots, offering an exceptional blend of flexibility and interpretability for abstracting low-level perceptual features. A widely adopted method within OCL is slot attention, which utilizes attention mechanisms to iteratively refine slot representations. However, a major draw-back of most object-centric models, including slot attention, is their reliance on predefining the number of slots. This not only necessitates prior knowledge of the dataset but also overlooks the inherent variability in the number of objects present in each instance. To overcome this fundamental limitation, we present a novel complexity-aware object auto-encoder framework. Within this framework, we introduce an adaptive slot attention (AdaSlot) mecha-nism that dynamically determines the optimal number of slots based on the content of the data. This is achieved by proposing a discrete slot sampling module that is responsible for selecting an appropriate number of slots from a candidate list. Furthermore, we introduce a masked slot decoder that suppresses unselected slots during the decoding process. Our framework, tested extensively on object discovery tasks with various datasets, shows performance matching or exceeding top fixed-slot models. Moreover, our analysis substantiates that our method exhibits the capability to dynamically adapt the slot number according to each instance's complexity, offering the potential for further exploration in slot attention research. Project will be available at https://kfan21.github.io/AdaSlot/}, author = {Fan, Ke and Bai, Zechen and Xiao, Tianjun and He, Tong and Horn, Max and Fu, Yanwei and Locatello, Francesco and Zhang, Zheng}, booktitle = {2024 IEEE/CVF Conference on Computer Vision and Pattern Recognition}, location = {Seattle, WA, United States}, publisher = {IEEE}, title = {{Adaptive slot attention: Object discovery with dynamic slot number}}, doi = {10.1109/cvpr52733.2024.02176}, year = {2024}, } @inproceedings{18956, abstract = {Group Activity Recognition (GAR) aims to detect the activity performed by multiple actors in a scene. Prior works model the spatio-temporal features based on the RGB, optical flow or keypoint data types. On the contrary, our hypothesis is that by only using the RGB data without temporality, the performance can be maintained with a negligible loss in accuracy. To that end, we propose a novel GAR technique for volleyball videos, DECOMPL, which consists of two complementary branches. In the visual branch, it extracts the features using attention pooling. In the coordinate branch, it considers the configuration of the players and extracts the spatial information from the box coordinates. Moreover, we analyzed the Volleyball dataset that the recent literature is mostly based on, and systematically reannotated it to emphasize the group concept. Experimental results demonstrated the effectiveness of the proposed model DECOMPL, which delivered the best/second best GAR performance with the reannotations/original annotations among the comparable state-of-the-art methods. Code and new annotations are available at GitHub: https://github.com/berkerdemirel/decompl}, author = {Demirel, Berker and Ozkan, Huseyin}, booktitle = {2024 IEEE International Conference on Image Processing}, issn = {2381-8549}, location = {Abu Dhabi, United Arab Emirates}, pages = {977--983}, publisher = {IEEE}, title = {{Decompl: Decompositional learning with attention pooling for group activity recognition from a single volleyball image}}, doi = {10.1109/icip51287.2024.10647499}, year = {2024}, } @inproceedings{14946, abstract = {We present a unified framework for studying the identifiability of representations learned from simultaneously observed views, such as different data modalities. We allow a partially observed setting in which each view constitutes a nonlinear mixture of a subset of underlying latent variables, which can be causally related. We prove that the information shared across all subsets of any number of views can be learned up to a smooth bijection using contrastive learning and a single encoder per view. We also provide graphical criteria indicating which latent variables can be identified through a simple set of rules, which we refer to as identifiability algebra. Our general framework and theoretical results unify and extend several previous work on multi-view nonlinear ICA, disentanglement, and causal representation learning. We experimentally validate our claims on numerical, image, and multi-modal data sets. Further, we demonstrate that the performance of prior methods is recovered in different special cases of our setup. Overall, we find that access to multiple partial views offers unique opportunities for identifiable representation learning, enabling the discovery of latent structures from purely observational data.}, author = {Yao, Dingling and Xu, Danru and Lachapelle, Sébastien and Magliacane, Sara and Taslakian, Perouz and Martius, Georg and Kügelgen, Julius von and Locatello, Francesco}, booktitle = {12th International Conference on Learning Representations}, location = {Vienna, Austria}, publisher = {Curran Associates}, title = {{Multi-view causal representation learning with partial observability}}, year = {2024}, } @article{17302, abstract = {The mountain cryosphere and groundwater play pivotal roles in shaping the hydrological cycle, yet their connectivity remains incompletely understood. Current knowledge on meltwater recharge and consequent groundwater discharge processes is better developed for snow–groundwater connectivity than for glacier–groundwater connectivity. Estimates of meltwater recharge vary considerably, which is probably a function of not only inherent catchment characteristics but also of the different spatio-temporal scales involved and the uncertainties in the methods used. This hinders a comprehensive understanding of the mountain water cycle. As glaciers retreat, permafrost thaws and snowpack diminishes, the relative importance of mountain groundwater is expected to increase. However, shifting and declining recharge from the cryosphere may decrease absolute groundwater amounts and fluxes with as-yet unknown effects on catchment-scale hydrological processes. We therefore stress the need to better quantify mountain cryosphere–groundwater connectivity to predict climate change impacts on mountain water supply and to support sustainable water resource management of downstream socio-ecological systems.}, author = {van Tiel, Marit and Aubry-Wake, Caroline and Somers, Lauren and Andermann, Christoff and Avanzi, Francesco and Baraer, Michel and Chiogna, Gabriele and Daigre, Clémence and Das, Soumik and Drenkhan, Fabian and Farinotti, Daniel and Fyffe, Catriona Louise and de Graaf, Inge and Hanus, Sarah and Immerzeel, Walter and Koch, Franziska and McKenzie, Jeffrey M. and Müller, Tom and Popp, Andrea L. and Saidaliyeva, Zarina and Schaefli, Bettina and Schilling, Oliver S. and Teagai, Kapiolani and Thornton, James M. and Yapiyev, Vadim}, issn = {2731-6084}, journal = {Nature Water}, pages = {624--637}, publisher = {Springer Nature}, title = {{Cryosphere–groundwater connectivity is a missing link in the mountain water cycle}}, doi = {10.1038/s44221-024-00277-8}, volume = {2}, year = {2024}, } @inproceedings{18971, abstract = {Models prone to spurious correlations in training data often produce brittle predictions and introduce unintended biases. Addressing this challenge typically involves methods relying on prior knowledge and group annotation to remove spurious correlations, which may not be readily available in many applications. In this paper, we establish a novel connection between unsupervised object-centric learning and mitigation of spurious correlations. Instead of directly inferring subgroups with varying correlations with labels, our approach focuses on discovering concepts: discrete ideas that are shared across input samples. Leveraging existing object-centric representation learning, we introduce CoBalT: a concept balancing technique that effectively mitigates spurious correlations without requiring human labeling of subgroups. Evaluation across the benchmark datasets for sub-population shifts demonstrate superior or competitive performance compared state-of-the-art baselines, without the need for group annotation. Code is available at https://github.com/rarefin/CoBalT}, author = {Arefin, Rifat and Zhang, Yan and Baratin, Aristide and Locatello, Francesco and Rish, Irina and Liu, Dianbo and Kawaguchi, Kenji}, booktitle = {Proceedings of the 41st International Conference on Machine Learning}, issn = {2640-3498}, location = {Vienna, Austria}, pages = {1672--1688}, publisher = {ML Research Press}, title = {{Unsupervised concept discovery mitigates spurious correlations}}, volume = {235}, year = {2024}, } @article{14938, abstract = {High elevation headwater catchments are complex hydrological systems that seasonally buffer water and release it in the form of snow and ice melt, modulating downstream runoff regimes and water availability. In High Mountain Asia (HMA), where a wide range of climates from semi-arid to monsoonal exist, the importance of the cryospheric contributions to the water budget varies with the amount and seasonal distribution of precipitation. Losses due to evapotranspiration and sublimation are to date largely unquantified components of the water budget in such catchments, although they can be comparable in magnitude to glacier melt contributions to streamflow. 
Here, we simulate the hydrology of three high elevation headwater catchments in distinct climates in HMA over 10 years using an ecohydrological model geared towards high-mountain areas including snow and glaciers, forced with reanalysis data. 
Our results show that evapotranspiration and sublimation together are most important at the semi-arid site, Kyzylsu, on the northernmost slopes of the Pamir mountain range. Here, the evaporative loss amounts to 28% of the water throughput, which we define as the total water added to, or removed from the water balance within a year. In comparison, evaporative losses are 19% at the Central Himalayan site Langtang and 13% at the wettest site, 24K, on the Southeastern Tibetan Plateau. At the three sites, respectively, sublimation removes 15%, 13% and 6% of snowfall, while evapotranspiration removes the equivalent of 76%, 28% and 19% of rainfall. In absolute terms, and across a comparable elevation range, the highest ET flux is 413 mm yr-1 at 24K, while the highest sublimation flux is 91 mm yr-1 at Kyzylsu. During warm and dry years, glacier melt was found to only partially compensate for the annual supply deficit.}, author = {Fugger, Stefan and Shaw, Thomas and Jouberton, Achille and Miles, Evan and Buri, Pascal and McCarthy, Michael and Fyffe, Catriona Louise and Fatichi, Simone and Kneib, Marin and Molnar, Peter and Pellicciotti, Francesca}, issn = {1748-9326}, journal = {Environmental Research Letters}, keywords = {Public Health, Environmental and Occupational Health, General Environmental Science, Renewable Energy, Sustainability and the Environment}, publisher = {IOP Publishing}, title = {{Hydrological regimes and evaporative flux partitioning at the climatic ends of High Mountain Asia}}, doi = {10.1088/1748-9326/ad25a0}, volume = {19}, year = {2024}, } @article{15298, abstract = {Mountains are important suppliers of freshwater to downstream areas, affecting large populations in particular in High Mountain Asia (HMA). Yet, the propagation of water from HMA headwaters to downstream areas is not fully understood, as interactions in the mountain water cycle between the cryo-, hydro- and biosphere remain elusive. We review the definition of blue and green water fluxes as liquid water that contributes to runoff at the outlet of the selected domain (blue) and water lost to the atmosphere through vapor fluxes, that is evaporation from water, ground, and interception plus transpiration (green) and propose to add the term white water to account for the (often neglected) evaporation and sublimation from snow and ice. We provide an assessment of models that can simulate the cryo-hydro-biosphere continuum and the interactions between spheres in high mountain catchments, going beyond disciplinary separations. Land surface models are uniquely able to account for such complexity, since they solve the coupled fluxes of water, energy, and carbon between the land surface and atmosphere. Due to the mechanistic nature of such models, specific variables can be compared systematically to independent remote sensing observations – providing vital insights into model accuracy and enabling the understanding of the complex watersheds of HMA. We discuss recent developments in spaceborne earth observation products that have the potential to support catchment modeling in high mountain regions. We then present a pilot study application of the mechanistic land surface model Tethys & Chloris to a glacierized watershed in the Nepalese Himalayas and discuss the use of high-resolution earth observation data to constrain the meteorological forcing uncertainty and validate model results. We use these insights to highlight the remaining challenges and future opportunities that remote sensing data presents for land surface modeling in HMA.}, author = {Buri, Pascal and Fatichi, Simone and Shaw, Thomas and Fyffe, Catriona Louise and Miles, Evan S. and Mccarthy, Michael and Kneib, Marin and Ren, Shaoting and Jouberton, Achille and Fugger, Stefan and Jia, Li and Zhang, Jing and Shen, Cong and Zheng, Chaolei and Menenti, Massimo and Pellicciotti, Francesca}, issn = {1009-5020}, journal = {Geo-Spatial Information Science}, number = {3}, pages = {703--727}, publisher = {Taylor & Francis}, title = {{Land surface modeling informed by earth observation data: Toward understanding blue–green–white water fluxes in High Mountain Asia}}, doi = {10.1080/10095020.2024.2330546}, volume = {27}, year = {2024}, } @article{14885, abstract = {The near-surface boundary layer can mediate the response of mountain glaciers to external climate, cooling the overlying air and promoting a density-driven glacier wind. The fundamental processes are conceptually well understood, though the magnitudes of cooling and presence of glacier winds are poorly quantified in space and time, increasing the forcing uncertainty for melt models. We utilize a new data set of on-glacier meteorological measurements on three neighboring glaciers in the Swiss Alps to explore their distinct response to regional climate under the extreme 2022 summer. We find that synoptic wind origins and local terrain modifications, not only glacier size, play an important role in the ability of a glacier to cool the near-surface air. Warm air intrusions from valley or synoptically-driven winds onto the glacier can occur between ∼19% and 64% of the time and contribute between 3% and 81% of the total sensible heat flux to the surface during warm afternoon hours, depending on the fetch of the glacier flowline and its susceptibility to boundary layer erosion. In the context of extreme summer warmth, indicative of future conditions, the boundary layer cooling (up to 6.5°C cooler than its surroundings) and resultant katabatic wind flow are highly heterogeneous between the study glaciers, highlighting the complex and likely non-linear response of glaciers to an uncertain future.}, author = {Shaw, Thomas and Buri, Pascal and Mccarthy, Michael and Miles, Evan S. and Pellicciotti, Francesca}, issn = {2169-8996}, journal = {Journal of Geophysical Research: Atmospheres}, number = {2}, publisher = {Wiley}, title = {{Local controls on near-surface glacier cooling under warm atmospheric conditions}}, doi = {10.1029/2023JD040214}, volume = {129}, year = {2024}, } @article{18628, abstract = {Arctic tidewater glaciers are retreating, serving as key indicators of global warming. This study aims to assess how subglacial hydrology affects glacier front retreat by comparing two glacier–fjord models of the Hansbreen glacier: one incorporating a detailed subglacial hydrology model and another simplifying the subglacial discharge to a single channel centered in the flow line. We first validate the subglacial hydrology model by comparing its discharge channels with observations of plume activity. Simulations conducted from April to December 2010 revealed that the glacier front position aligns more closely with the observations in the coupled model than in the simplified version. Furthermore, the mass loss due to calving and submarine melting is greater in the coupled model, with the calving mass loss reaching 6 Mt by the end of the simulation compared to 4 Mt in the simplified model. These findings highlight the critical role of subglacial hydrology in predicting glacier dynamics and emphasize the importance of detailed modeling in understanding the responses of Arctic tidewater glaciers to climate change.}, author = {De Andrés, Eva and Muñoz Hermosilla, José M and Shahateet, Kaian and Otero, Jaime}, issn = {2306-5338}, journal = {Hydrology}, number = {11}, publisher = {MDPI}, title = {{The importance of solving Subglaciar hydrology in modeling glacier retreat: A case study of Hansbreen, Svalbard}}, doi = {10.3390/hydrology11110193}, volume = {11}, year = {2024}, } @article{15362, abstract = {Constitutional heterozygous pathogenic variants in the exonuclease domain of POLE and POLD1, which affect the proofreading activity of the corresponding polymerases, cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally accepted explanation for the connection between the disruption of the proofreading activity of polymerases epsilon and delta and cancer development is through an increase in the somatic mutation rate. Here we studied an extended family with multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro), which segregates with the polyposis and cancer phenotypes. Through the analysis of mutational patterns of patient-derived fibroblasts colonies and de novo mutations obtained by parent-offspring comparisons, we concluded that heterozygous POLD1 L474P just subtly increases the somatic and germline mutation burden. In contrast, tumors developed in individuals with a heterozygous mutation in the exonuclease domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb) associated with signature SBS10d. We solved this contradiction through the observation that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele. These results imply that exonuclease deficiency of polymerase delta has a recessive effect on mutation rate.}, author = {Andrianova, Maria A. and Seplyarskiy, Vladimir B. and Terradas, Mariona and Sánchez-Heras, Ana Beatriz and Mur, Pilar and Soto, José Luis and Aiza, Gemma and Borràs, Emma and Kondrashov, Fyodor and Kondrashov, Alexey S. and Bazykin, Georgii A. and Valle, Laura}, issn = {1476-5438}, journal = {European Journal of Human Genetics}, pages = {837--845}, publisher = {Springer Nature}, title = {{Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells}}, doi = {10.1038/s41431-024-01598-8}, volume = {32}, year = {2024}, } @article{15179, abstract = {The fungal bioluminescence pathway can be reconstituted in other organisms allowing luminescence imaging without exogenously supplied substrate. The pathway starts from hispidin biosynthesis—a step catalyzed by a large fungal polyketide synthase that requires a posttranslational modification for activity. Here, we report identification of alternative compact hispidin synthases encoded by a phylogenetically diverse group of plants. A hybrid bioluminescence pathway that combines plant and fungal genes is more compact, not dependent on availability of machinery for posttranslational modifications, and confers autonomous bioluminescence in yeast, mammalian, and plant hosts. The compact size of plant hispidin synthases enables additional modes of delivery of autoluminescence, such as delivery with viral vectors.}, author = {Palkina, Kseniia A. and Karataeva, Tatiana A. and Perfilov, Maxim M. and Fakhranurova, Liliia I. and Markina, Nadezhda M. and Gonzalez Somermeyer, Louisa and Garcia-Perez, Elena and Vazquez-Vilar, Marta and Rodriguez-Rodriguez, Marta and Vazquez-Vilriales, Victor and Shakhova, Ekaterina S. and Mitiouchkina, Tatiana and Belozerova, Olga A. and Kovalchuk, Sergey I. and Alekberova, Anna and Malyshevskaia, Alena K. and Bugaeva, Evgenia N. and Guglya, Elena B. and Balakireva, Anastasia and Sytov, Nikita and Bezlikhotnova, Anastasia and Boldyreva, Daria I. and Babenko, Vladislav V. and Kondrashov, Fyodor and Choob, Vladimir V. and Orzaez, Diego and Yampolsky, Ilia V. and Mishin, Alexander S. and Sarkisyan, Karen S.}, issn = {2375-2548}, journal = {Science Advances}, number = {10}, publisher = {American Association for the Advancement of Science}, title = {{A hybrid pathway for self-sustained luminescence}}, doi = {10.1126/sciadv.adk1992}, volume = {10}, year = {2024}, } @article{18779, abstract = {Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here, we propose a spatial autocorrelation method based on Local Moran’s I coefficient to differentiate signal, background, and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Moran’s method outperforms threshold-based method in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the method’s power in real situation, we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage-gated potassium channels in mice. Moran’s method identified high-intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage-gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Moran’s method is a rapid, simple image segmentation method optimal for variable and high noise conditions.}, author = {Dávid, Csaba and Giber, Kristóf and Szigeti, Margit Katalin and Köllő, Mihály and Nusser, Zoltan and Acsady, Laszlo}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{A novel image segmentation method based on spatial autocorrelation identifies A-type potassium channel clusters in the thalamus}}, doi = {10.7554/elife.89361}, volume = {12}, year = {2024}, } @article{17331, abstract = {Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened the possibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet structure. Exploiting the comprehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine.}, author = {Cattaneo, Elizabeth R and Gisonno, Romina A and Abba, Martín C and Santana, Marianela and Rosú, Silvana A and Nucifora, Elsa and Aguirre, María A and Giordani, María C and Tricerri, M. Alejandra and Ramella, Nahuel A}, issn = {1097-0134}, journal = {Proteins: Structure, Function and Bioinformatics}, number = {12}, pages = {1366--1374}, publisher = {Wiley}, title = {{Hereditary amyloidosis: Insights into a fibrinogen A variant protein}}, doi = {10.1002/prot.26732}, volume = {92}, year = {2024}, } @article{17091, abstract = {DNA sequences are connected to genes and functions in the developing and adult brain}, author = {Novarino, Gaia and Bock, Christoph}, issn = {1095-9203}, journal = {Science}, number = {6698}, pages = {860--861}, publisher = {AAAS}, title = {{Mapping the brain’s gene-regulatory maze}}, doi = {10.1126/science.adp4663}, volume = {384}, year = {2024}, } @article{18307, abstract = {Vaccination is the most effective tool to control infectious diseases. However, the evolution of vaccine resistance, exemplified by vaccine resistance in SARS-CoV-2, remains a concern. Here, we model complex vaccination strategies against a pathogen with multiple epitopes—molecules targeted by the vaccine. We found that a vaccine targeting one epitope was ineffective in preventing vaccine escape. Vaccine resistance in highly infectious pathogens was prevented by the full-epitope vaccine, that is, one targeting all available epitopes, but only when the rate of pathogen evolution was low. Strikingly, a bet-hedging strategy of random administration of vaccines targeting different epitopes was the most effective in preventing vaccine resistance in pathogens with the low rate of infection and high rate of evolution. Thus, complex vaccination strategies, when biologically feasible, may be preferable to the currently used single-vaccine approaches for long-term control of disease outbreaks, especially when applied to livestock with near 100% vaccination rates.}, author = {Rella, Simon and Kulikova, Yuliya A. and Minnegalieva, Aygul and Kondrashov, Fyodor}, issn = {1558-5646}, journal = {Evolution: International journal of organic evolution}, number = {10}, pages = {1722--1738}, publisher = {Oxford University Press}, title = {{Complex vaccination strategies prevent the emergence of vaccine resistance}}, doi = {10.1093/evolut/qpae106}, volume = {78}, year = {2024}, } @article{14793, abstract = {Superconductor/semiconductor hybrid devices have attracted increasing interest in the past years. Superconducting electronics aims to complement semiconductor technology, while hybrid architectures are at the forefront of new ideas such as topological superconductivity and protected qubits. In this work, we engineer the induced superconductivity in two-dimensional germanium hole gas by varying the distance between the quantum well and the aluminum. We demonstrate a hard superconducting gap and realize an electrically and flux tunable superconducting diode using a superconducting quantum interference device (SQUID). This allows to tune the current phase relation (CPR), to a regime where single Cooper pair tunneling is suppressed, creating a sin(2y) CPR. Shapiro experiments complement this interpretation and the microwave drive allows to create a diode with ≈ 100% efficiency. The reported results open up the path towards integration of spin qubit devices, microwave resonators and (protected) superconducting qubits on the same silicon technology compatible platform.}, author = {Valentini, Marco and Sagi, Oliver and Baghumyan, Levon and de Gijsel, Thijs and Jung, Jason and Calcaterra, Stefano and Ballabio, Andrea and Aguilera Servin, Juan L and Aggarwal, Kushagra and Janik, Marian and Adletzberger, Thomas and Seoane Souto, Rubén and Leijnse, Martin and Danon, Jeroen and Schrade, Constantin and Bakkers, Erik and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Parity-conserving Cooper-pair transport and ideal superconducting diode in planar germanium}}, doi = {10.1038/s41467-023-44114-0}, volume = {15}, year = {2024}, }