Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellum’s expansion during human evolution, yet they remain largely unexplored. In this study, we combined single-nucleus measurements of gene expression and chromatin accessibility from six mammals (human, bonobo, macaque, marmoset, mouse, and opossum) to uncover conserved and diverged regulatory networks in cerebellum development. We identified core regulators of cell identity and developed sequence-based models that revealed conserved regulatory codes. By predicting chromatin accessibility across 240 mammalian species, we reconstructed the evolutionary histories of human cis-regulatory elements, identifying sets associated with positive selection and gene expression changes, including the recent gain of THRB expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.

Background: Comprehensive and evidence-based countermeasures against emerging infectious diseases have become increasingly important in recent years. COVID-19 and many other infectious diseases are spread by human movement and contact, but complex transportation networks in the 21st century make it difficult to predict disease spread in rapidly changing situations. It is especially challenging to estimate the network of infection transmission in countries where traffic and human movement data infrastructure is not yet developed. Methods: In this study, we devised a method utilizing an ordinary and partial differential equations-based mathematical model and a modified mathematical optimization method to estimate the network of transmission of COVID-19 from the time series data of its infection and applied it to determine its spread across areas in Japan. Furthermore, utilizing the estimated human mobility network, we predicted the spread of infection using the Tokyo Olympics as a model. Findings: We incorporated the effects of soft lockdowns, such as the declaration of a state of emergency, and changes in the infection network due to government-sponsored travel promotion, and revealed that the estimated effective distance captured human mobility changing dynamically in the different stages of the pandemic. The model predicted that the Tokyo Olympic and Paralympic Games would increase the number of infected cases in the host prefectures by up to 80%. Interpretation: The models used in this study are available online, and our data-driven infection network models are scalable, whether it be at the level of a city, town, country, or continent, and applicable anywhere in the world, as long as the time-series data of infections per region is available. These estimations of effective distance and the depiction of infectious disease networks based on actual infection data are expected to be useful in devising data-driven countermeasures against emerging infectious diseases worldwide.

Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellum’s expansion during human evolution, yet they remain largely unexplored. In this study, we combined single-nucleus measurements of gene expression and chromatin accessibility from six mammals (human, bonobo, macaque, marmoset, mouse, and opossum) to uncover conserved and diverged regulatory networks in cerebellum development. We identified core regulators of cell identity and developed sequence-based models that revealed conserved regulatory codes. By predicting chromatin accessibility across 240 mammalian species, we reconstructed the evolutionary histories of human cis -regulatory elements, identifying sets associated with positive selection and gene expression changes, including the recent gain of THRB expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.

The mechanism of temporal differences in development between species – developmental allochrony – has been elusive. These authors demonstrate that multiple biochemical reaction parameters, especially degradation and expression rates, can explain the allochrony of the human and mouse segmentation clocks. In addition to this fascinating scientific question, we recommend this article because of the three following points: (1) the authors established an experimental system to investigate temporal differences in developmental processes between species; (2) they thoroughly measured the biochemical parameters of the reaction; (3) they described the possible mechanism of allochrony using a simple, classical mathematical model of biochemical reactions combined with measured parameters. This study has taken an essential step in understanding the various time scales of interspecies development.

It was difficult to perturb a local network and evaluate its roles. The authors combined mathematical models and calcium imaging and found that the ablation of a small number of neurons with similar receptive fields significantly reduces responses to stimuli. I’m recommending this article because the authors used network models quite effectively to make a valid prediction and conducted elaborate experiments to test the hypothesis: 1) mapping of neuronal selectivity and 2) photoablation of particular neurons in layer 2/3. This research made an important step toward understanding the roles of cortical circuitry in information processing in the brain.

Sleep spindles are distinctive EEG waves during NREM sleep, with the frequency in the range 9-15 Hz. Altought the thalamocortical (TC) system is considered as a main source of sleep spindles, several studies indicate that also cortical interneurons may play pivotal roles in generating sleep spindles.Here, we hypothesized that a certain firing pattern in cortical interneurons is essential for sleep spindles generation, and developed a minimum computational model of an inhibitory cortical neuron with five channels and a pump, which recapitulates the firing pattern of cortical neurons during sleep spindles. Comprehensive bifurcation and detailed mathematical analyses predicted that one channel family play a role in generating the electrophysiological characteristics of sleep spindles. Then, we generated transgenic mice and analyzed sleep spindles from EEG data. As a result, a part of transgenic mice showed decreased sleep spindles episode and events. Combining these two approaches, we suggest a novel mechanism of sleep spindles generation, which may become a potential target for a treatment or a biomarker of certain diseases related to sleep spindles, like schizophrenia or absence seizure.