by Bingxian Xu, Dae-Sung Hwangbo, Sumit Saurabh, Clark Rosensweig, Ravi Allada, William L. Kath, Rosemary Braun The circadian clock is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce circadian oscillations in thousands of genes in a tissue–specific manner, orchestrating myriad biological processes. While previous studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations o ..read more

by Emma Beniston, Jordan P. Skittrall Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frame ..read more

by Florian G. Pflug, Simon Haendeler, Christopher Esk, Dominik Lindenhofer, Jürgen A. Knoblich, Arndt von Haeseler Neural organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progenies arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This high variability exceeds what can be explained by existing stochastic models of corticogenesis and indicates the existence of an additional source of stochasticity. To expl ..read more

by Alejandro Tlaie, Katharine Shapcott, Thijs L. van der Plas, James Rowland, Robert Lees, Joshua Keeling, Adam Packer, Paul Tiesinga, Marieke L. Schölvinck, Martha N. Havenith Trial-averaged metrics, e.g. tuning curves or population response vectors, are a ubiquitous way of characterizing neuronal activity. But how relevant are such trial-averaged responses to neuronal computation itself? Here we present a simple test to estimate whether average responses reflect aspects of neuronal activity that contribute to neuronal processing. The test probes two assumptions implicitly made whenever avera ..read more

by Anastasis Oulas, Kyriaki Savva, Nestoras Karathanasis, George M. Spyrou Prioritization or ranking of different cell types in a Single-cell RNA Sequencing (scRNA-Seq) framework can be performed in a variety of ways, some of these include: i) obtaining an indication of the proportion of cell types between the different conditions under study, ii) counting the number of differentially expressed genes (DEGs) between cell types and conditions in the experiment or, iii) prioritizing cell types based on prior knowledge about the conditions under study (i.e., a specific disease). These methods have ..read more

by Kamil Wołos, Leszek Pstras, Malgorzata Debowska, Wojciech Dabrowski, Dorota Siwicka-Gieroba, Jan Poleszczuk Cardiovascular diseases are the leading cause of death globally, making the development of non-invasive and simple-to-use tools that bring insights into the state of the cardiovascular system of utmost importance. We investigated the possibility of using peripheral pulse wave recordings to estimate stroke volume (SV) and subject-specific parameters describing the selected properties of the cardiovascular system. Peripheral pressure waveforms were recorded in the radial artery using ap ..read more

by Danica Despotović, Corentin Joffrois, Olivier Marre, Matthew Chalk The efficient coding hypothesis posits that early sensory neurons transmit maximal information about sensory stimuli, given internal constraints. A central prediction of this theory is that neurons should preferentially encode stimuli that are most surprising. Previous studies suggest this may be the case in early visual areas, where many neurons respond strongly to rare or surprising stimuli. For example, previous research showed that when presented with a rhythmic sequence of full-field flashes, many retinal ganglion cells ..read more

by Satyaki Roy, Shehzad Z. Sheikh, Terrence S. Furey Network inference is used to model transcriptional, signaling, and metabolic interactions among genes, proteins, and metabolites that identify biological pathways influencing disease pathogenesis. Advances in machine learning (ML)-based inference models exhibit the predictive capabilities of capturing latent patterns in genomic data. Such models are emerging as an alternative to the statistical models identifying causative factors driving complex diseases. We present CoVar, an ML-based framework that builds upon the properties of existing in ..read more

by Carolin Zitzmann, Ruian Ke, Ruy M. Ribeiro, Alan S. Perelson Mathematical models of viral infection have been developed, fitted to data, and provide insight into disease pathogenesis for multiple agents that cause chronic infection, including HIV, hepatitis C, and B virus. However, for agents that cause acute infections or during the acute stage of agents that cause chronic infections, viral load data are often collected after symptoms develop, usually around or after the peak viral load. Consequently, we frequently lack data in the initial phase of viral growth, i.e., when pre-symptomatic ..read more

by Arco Bast, Rieke Fruengel, Christiaan P. J. de Kock, Marcel Oberlaender Neurons in the cerebral cortex receive thousands of synaptic inputs per second from thousands of presynaptic neurons. How the dendritic location of inputs, their timing, strength, and presynaptic origin, in conjunction with complex dendritic physiology, impact the transformation of synaptic input into action potential (AP) output remains generally unknown for in vivo conditions. Here, we introduce a computational approach to reveal which properties of the input causally underlie AP output, and how this neuronal input-ou ..read more