Science Society

Dr. Anna Schroeder, a leading neuroscientist, graces our show in this episode to shed light on a crucial yet understudied facet of neocortical circuits. Top-down projections in our brain act as a bridge between previous experiences, current objectives, and the sensory neocortex, playing a pivotal role in our perception and memory. While excitatory pathways have been typically associated with top-down control, inhibitory top-down projections remain a largely uncharted territory.Dr. Schroeder's ground-breaking research, employing a unique blend of synaptic two-photon calcium imaging, circuit mapping, cortex-dependent learning, and chemogenetics in mice, uncovers the GABAergic afferents from the subthalamic zona incerta as a significant source of top-down input to the neocortex. The zona incerta's inhibitory projections are critical for learning, as they transmit integrated top-down information that is essential for encoding sensory stimuli.Perhaps the most striking revelation from Dr. Schroeder's research is the bidirectional encoding of learned top-down relevance by the incertocortical afferents, which stands out from traditional excitatory pathways. These afferents form a disinhibitory circuit, and it is the swift appearance of negative responses that primarily drives changes in stimulus representation.Through her findings, Dr. Schroeder provides a compelling perspective on the unique contribution of long-range (dis)inhibitory afferents to the computational flexibility of neocortical circuits.Dr. Anna Schroeder, Neocortical Circuits, GABAergic Afferents, Zona Incerta, Top-Down Projections, Sensory Neocortex, Two-Photon Calcium Imaging, Circuit Mapping, Cortex-Dependent Learning, Chemogenetics, Disinhibitory Circuit.Inhibitory top-down projections from zona incerta mediate neocortical memory https://doi.org/10.1016/j.neuron.2022.12.010

In this fascinating episode, Dr. McConohy dives deep into the intricacies of solid electrolytes in rechargeable lithium-metal batteries, and how they are susceptible to short-circuiting during plating. He presents a comprehensive investigation into the effect of both locally and globally applied stress on lithium penetration initiation in LLZO (Li6.6La3Ta0.4Zr1.6O12), using the method of operando microprobe scanning electron microscopy. Dr. McConohy's detailed statistical analysis demonstrates that lithium intrusion follows a Weibull distribution, and intriguingly, he unveils how an increased microprobe-LLZO contact force can significantly reduce the characteristic failure diameter of lithium metal. Further, he talks about how the direction of intrusion propagation can be manipulated using a 0.070% compressive strain via operando cantilever beam-bending experiments. Tune in to understand the complex interplay of current focusing, nanoscale cracks, and their role in lithium intrusion into the electrolyte, providing valuable insights into the mechanical tunability of electrochemical plating reactions in brittle solid electrolytes.Lithium-metal batteries, Solid electrolytes, Lithium penetration, Stress, LLZO, Operando microprobe scanning electron microscopy, Weibull distribution, Intrusion propagation, Nanoscale cracks, Mechanical tunability, Electrochemical plating reactions.McConohy, G., Xu, X., Cui, T. et al. Mechanical regulation of lithium intrusion probability in garnet solid electrolytes. Nat Energy (2023). https://doi.org/10.1038/s41560-022-01186-4

In this enlightening episode, we are joined by Dr. Felsche who explores the pressing issue of prolonged heat periods that have become a prominent feature of European climate. Despite their recurrence, knowledge about the dominant spatial patterns of heatwaves and their impact on moisture-related processes remains sparse. Dr. Felsche discusses how gaining insights into these patterns could significantly improve heatwave and drought prediction, and thus lead to effective mitigation strategies. He describes how they used hierarchical agglomerative clustering to determine nine dominant spatial heatwave patterns based on a 50-member regional climate model (Canadian Regional Climate Model version 5, CRCM5-LE). Interestingly, these patterns align well with clusters derived from an observational dataset (E-OBS) and with records of extreme historical heatwave events. Dr. Felsche then delves into the intricate relationship between the occurrence of heatwaves and the soil moisture deficit present both before and after these events. Discover how negative soil moisture anomalies in the preceding winter/spring can act as a predictor for heatwaves in Southern Europe, and how North Europe exhibits a negative correlation between the number of heatwave days in summer and autumn soil moisture content. Join us as we unlock crucial understanding about the spatial patterns and environmental effects of heatwaves.Heatwaves, European climate, Spatial patterns, Moisture-related processes, Hierarchical agglomerative clustering, Regional climate model, CRCM5-LE, E-OBS, Soil moisture deficit, Drought prediction, Climate mitigation strategies.Felsche, E., Böhnisch, A. & Ludwig, R. Inter-seasonal connection of typical European heatwave patterns to soil moisture. npj Clim Atmos Sci 6, 1 (2023). https://doi.org/10.1038/s41612-023-00330-5

In this fascinating episode, we delve into the realm of bioarchaeology and genomics with Dr. Raquel Fleskes and Dr. Theodore Schurr. Their groundbreaking work, the Anson Street African Burial Ground Project, investigated the lives of thirty-six 18th-century individuals from Charleston, South Carolina. The duo provides insights into their research methods, and how they managed to generate low coverage genomic data from 18 of these individuals. This data unveiled a wide spectrum of ancestral connections across Western Africa, including one individual with genomic affiliations with the Fulani peoples of West Africa. This project represents the largest number of ancient genomes from African-descended persons in North America ever studied. It is a substantial leap forward in enhancing our understanding of African diversity and history in colonial America.Dr. Fleskes and Dr. Schurr further discuss the critical role of community-engaged research, and how their study, initiated in close collaboration with the Gullah Society of Charleston and other community members, exemplifies this practice. Join us as we unravel the complex tapestry of colonial histories and uncover the stories of these ancestors, previously obscured by time and oppression.Bioarchaeology, Genomics, Anson Street African Burial Ground Project, Colonial America, African diversity, Paleogenomics, Genetic origins, African-descendant populations, Community-engaged research, Gullah Society, West and West-Central African ancestry.Community-engaged ancient DNA project reveals diverse origins of 18th-century African descendants in Charleston, South Carolina https://doi.org/10.1073/pnas.2201620120

Join us in this enlightening episode as we chat with Dr. Gabert about his innovative work in the development of robotic leg prostheses. His pioneering research is set to enhance the mobility and quality of life of millions of individuals with lower-limb amputations.Dr. Gabert presents a unique robotic leg prosthesis that not only emulates the essential biomechanical functions of the biological knee, ankle, and toe, but also manages to match the weight, size, and battery life of conventional microprocessor-controlled prostheses. Learn about the impressive torque-sensitive mechanism powering the knee joint and the compliant, underactuated system operating the ankle and toe joints. These components allow for substantial mechanical energy regeneration and closely mimic the key biomechanical functions of the ankle/foot complex during walking. Dr. Gabert further elaborates on the practical aspects of this prosthesis, discussing how all mechanical and electrical components are enclosed within a compact frame for improved robustness and efficiency. With clinical tests showing promising results, this innovative prosthetic design holds the potential to significantly improve the real-world mobility of individuals with above-knee amputation.Robotic leg prosthesis, Biomechanics, Lower-limb amputations, Torque-sensitive mechanism, Underactuated system, Mechanical energy regeneration, Above-knee amputation, Robustness, Efficiency, Mobility improvement.A lightweight robotic leg prosthesis replicating the biomechanics of the knee, ankle, and toe joint https://doi.org/10.1126/scirobotics.abo3996

In this enlightening episode, Dr. Hermundur Sigmundsson delves into an innovative approach to improve reading skill development in children, based on his groundbreaking work in Iceland.His perspective, referred to as 'READ', incorporates the phonics approach to reading achievement, which emphasizes the importance of teaching children how to decipher the reading code. Additionally, 'READ' merges key concepts from theories of learning and skill development, such as 'deliberate practice' and 'flow'. Dr. Sigmundsson discusses how 'deliberate practice', a concept developed by Ericsson, involves baseline measurements that provide a foundation for follow-up and intentional practice. Coupled with the concept of 'flow', coined by Csikszentmihalyi, where challenges are always in relation to the skills, this ensures every child can experience a state of 'flow', feeling a sense of mastery and competence. He further explores how the training hour allows children to strengthen the neural network used for specific skills being trained, with letter-sound knowledge being practiced until the child has cracked the reading code. Dr. Sigmundsson shares promising results from the first-year trial in Vestmannaeyjar school in Iceland, where all the children were able to read simple words, 96% were able to read sentences, and 88% could read text. This episode invites an engaging discussion around Ericsson’s and Csikszentmihalyi’s influential theories and their application in reading skill development.Reading skill development, Phonics approach, Learning theories, Deliberate practice, Flow, Mastery, Neural network, Letter-sound knowledge, Reading code, Ericsson, Csikszentmihalyi.Sigmundsson, H.; Thórsdóttir, H.S.; Njálsdóttir, H.R.; Hjaltalín, S.T. Reading: From the Simple to the Complex. Brain Sci. 2022,12,1670. https://doi.org/10.3390/brainsci12121670

In this episode, Dr. Aleksandra Serafin shares her revolutionary work on using electroconductive scaffolds for spinal cord injury (SCI) repair. Despite the hostile environment post-SCI that hampers neuronal track re-establishment, her research is offering promising prospects for SCI tissue engineering (TE) treatment strategies.Dr. Serafin discusses the limitations of existing conductive polymers, like poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), due to their suboptimal biofunctionality and biocompatibility. She elucidates her innovative solution, synthesizing PEDOT nanoparticles (NPs) via chemical oxidation polymerization in miniemulsion, which are then incorporated with gelatin and hyaluronic acid (HA) to create gel:HA:PEDOT-NPs scaffolds.She shares her comprehensive study results, detailing scaffold characteristics including increased conductivity, controlled porosity, and a compressive modulus tailored to match the native spinal cord. Also noteworthy are the excellent 3D shear-thinning printing capabilities of the hydrogel and the superior shape fidelity post-printing.Highlighting in-vitro and in-vivo study outcomes, Dr. Serafin reveals how these scaffolds exhibit cytocompatibility and positively influence signal re-establishment and the initiation of healing mechanisms in a rat SCI model. In particular, the HA in the scaffold demonstrates immunomodulatory properties, controlling inflammatory response and limiting scar formation, thereby enhancing axonal migration towards the implantation site.Through her research, Dr. Serafin convincingly demonstrates the potential of gel:HA:PEDOT-NPs scaffolds as a promising TE solution for SCI regeneration, paving the way for future treatments.Key Words: Spinal Cord Injury, Electroconductive Scaffolds, Tissue Engineering, Conductive Polymers, PEDOT:PSS, PEDOT Nanoparticles, Gel:HA:PEDOT-NPs Scaffolds, Cytocompatibility, Axonal Migration, Hyaluronic Acid, Immunomodulatory Properties, Regeneration.Serafin, A., Rubio, M.C., Carsi, M. et al. Electroconductive PEDOT nanoparticle integrated scaffolds for spinal cord tissue repair. Biomater Res (2022). https://doi.org/10.1186/s40824-022-00310-5

In this enlightening episode, Dr. Martín-Zamora takes listeners on a deep dive into the complex world of larvae evolution and how temporal shifts in trunk formation underpin the diversification of larvae and bilaterian life cycles. Despite larvae's central role in animal evolution scenarios across all major animal lineages, the understanding of how larvae evolved remains elusive. Dr. Martín-Zamora's groundbreaking research seeks to fill this knowledge gap.Dr. Martín-Zamora presents his study, where chromosome-scale genome sequencing was performed on the annelid Owenia fusiformis, combined with transcriptomic and epigenomic profiling during the life cycles of this species and two other annelids. His research reveals that trunk development in O. fusiformis is postponed to pre-metamorphic stages in the feeding larva, in contrast to the non-feeding larva of Capitella teleta and the directly developing embryo of Dimorphilus gyrociliatus where it begins post-gastrulation.His findings also highlight that the embryos of O. fusiformis first develop into an enlarged anterior domain, forming larval tissues and the adult head. This is consistent with observations in the so-called 'head larvae' of other bilaterians, showing extensive transcriptomic similarities with the O. fusiformis larva.Dr. Martín-Zamora posits that the temporal decoupling of head and trunk formation seen in head larvae may have facilitated larval evolution in Bilateria. This new perspective offers an intriguing departure from traditional theories that attribute larva and adult origins to co-option or innovation of gene regulatory programs.Key Words: Larvae Evolution, Bilaterian Life Cycles, Temporal Shifts, Trunk Formation, Annelids, Owenia fusiformis, Genome Sequencing, Transcriptomic Profiling, Epigenomic Profiling, Head Larvae, Gene Regulatory Programs, Animal Evolution.Martín-Zamora, F.M., Liang, Y., Guynes, K. et al. Annelid functional genomics reveals the origins of bilaterian life cycles. Nature (2023). https://doi.org/10.1038/s41586-022-05636-7

In this exciting episode, Dr. Long Zhang discusses his groundbreaking research on developing a molecular electric motor. The conversation explores the implications and potential of such technology, especially considering the vast influence of macroscopic electric motors on modern society.Dr. Zhang shares details about the construction of a molecular electric motor based on a [3]catenane, which involves two cyclobis(paraquat-p-phenylene) (CBPQT4+) rings powered by electricity to circumrotate unidirectionally around a 50-membered loop. The motor's design ensures that both rings perform highly unidirectional movement, guided by a flashing energy ratchet.The conversation deepens as Dr. Zhang explains the mechanism behind the unidirectional movement, powered by an oscillating voltage or external modulation of the redox potential. Although initial efforts on a homologous [2]catenane proved insufficient to support unidirectional movement, the incorporation of a second CBPQT4+ ring provided the necessary symmetry breaking.The significant achievement of Dr. Zhang's research lies in its waste-free operation, a unique aspect of these electric molecular motors. This development represents an essential stride towards the actualization of surface-bound electric molecular motors, holding potential implications for a range of technologies and industries.Key Words: Molecular Motors, Electric Motors, [3]Catenane, Cyclobis(paraquat-p-phenylene), Unidirectional Movement, Flashing Energy Ratchet, Oscillating Voltage, Redox Potential, Symmetry Breaking, Electrically Driven Circumrotatory Motion, Surface-Bound Electric Molecular Motors.Zhang, L., Qiu, Y., Liu, WG. et al. An electric molecular motor. Nature 613, 280–286 (2023). https://doi.org/10.1038/s41586-022-05421-6

Dr. Aneesh Bose joins us in this insightful episode to discuss the growing problem of pharmaceutical pollution and its potential impact on ecosystems worldwide. With pharmaceutical drugs increasingly detected in wildlife tissues, Dr. Bose highlights the urgent need to understand the effects of these pollutants on natural ecosystems.This episode dives into Dr. Bose's innovative research involving larval odonates (dragonfly and damselfly nymphs). His team investigated the effects of exposure to two pharmaceuticals, cetirizine and citalopram, and their combination on predator-prey interactions. Dr. Bose shares fascinating findings, which showed that exposure to both compounds increased dragonfly activity and influenced their predation success and efficiency in complex ways. He explains that while citalopram exposure reduced predation efficiency, cetirizine exposure led to diverse effects, enhancing predation success in some contexts but impairing it in others.These findings emphasize the importance of examining the effects of pharmaceuticals in various contexts. Furthermore, Dr. Bose explains how such compounds can alter predator-prey outcomes, even at sublethal concentrations. Tune in to learn more about this emerging environmental threat and how it can reshape our understanding of ecosystem dynamics.Key Words: Pharmaceutical Pollution, Ecosystems, Predator-Prey Interactions, Odonate Nymphs, Cetirizine, Citalopram, Predation Efficiency, Sublethal Concentrations, Environmental Threat, Dragonflies, Damselflies.Pharmaceutical pollution disrupts the behavior and predator-prey interactions of two widespread aquatic insects https://doi.org/10.1016/j.isci.2022.105672

In this episode, we welcome Dr. Susanne Rafelski, a leading expert in cellular organization, to explore the complex interplay between gene expression and cellular phenotype. The challenge of understanding how a subset of expressed genes influences cellular phenotype is daunting due to the sheer number of involved molecules, their combinations, and the multitude of cellular behaviors they determine.Dr. Rafelski's research reduces this complexity by focusing on cellular organization—a critical determinant and indicator of cell behavior. She introduces the WTC-11 hiPSC Single-Cell Image Dataset v1, a remarkable dataset containing over 200,000 live 3D cells across 25 key cellular structures. The scale and quality of this dataset have allowed for the creation of a comprehensive analysis framework to convert raw image data into dimensionally reduced, human-interpretable, quantitative measurements, promoting data exploration.Dr. Rafelski talks us through how this framework harnesses the vast cell-to-cell variability seen within a normal population, integrates cell-by-cell structural data, and supports quantitative analyses of distinct aspects of organization within and across cell populations. Her team found that the integrated intracellular organization of interphase cells remained robust amidst the wide range of variation in cell shape in the population. Furthermore, the average locations of some structures became polarized in cells at the colony edges while maintaining their 'wiring' with other structures. Join us as we delve into the fascinating world of cellular organization and discover how changes in structure location during early mitotic reorganization are accompanied by changes in their wiring.Key Words: Cellular Organization, Gene Expression, Cellular Phenotype, WTC-11 hiPSC Single-Cell Image Dataset v1, Data Analysis Framework, Cell Variability, Structural Data, Mitotic Reorganization.Viana, M.P., Chen, J., Knijnenburg, T.A. et al. Integrated intracellular organization and its variations in human iPS cells. Nature 613, 345–354 (2023). https://doi.org/10.1038/s41586-022-05563-7 Slides: https://docs.google.com/presentation/d/1VO2SUjtnPV-6GvXboP1Uap1G2hKtSux0PEUoQwT7760/edit#slide=id.p1

In this episode, we speak with Dr. Vales-Colomer, a leading researcher in the field of microbiome science. Our conversation revolves around the human microbiome, its integral role in health, and the profound influence of interpersonal relationships on its genetic makeup. Dr. Vales-Colomer delves into his latest research, based on an analysis of over 9,700 human metagenomes. This study reveals the intricate patterns of bacterial strain transmission between individuals, demonstrating the significant role of mother-to-infant transmission, intra-household sharing, and intra-population patterns. His findings suggest that approximately half of the bacterial strains in an infant's gut microbiome are transmitted from their mother, and this transmission remains detectable even in later life stages.The conversation also touches upon the oral microbiome and the horizontal transmission that largely defines its makeup. Dr. Vales-Colomer highlights how cohabitation length influences strain sharing more significantly than age or genetics. Fascinatingly, his research also shows that bacterial strain-sharing patterns can better illustrate host population structures than species-level profiles.Finally, Dr. Vales-Colomer discusses the identification of specific taxa that appear efficient in spreading across different transmission modes and their associated bacterial phenotypes linked to out-of-host survival capabilities. Tune in to this episode for a fascinating journey into the world of the human microbiome and learn about the deep interplay between our microbes and social dynamics.Key Words: Human Microbiome, Health, Interpersonal Relationships, Bacterial Strain Transmission, Mother-to-Infant Transmission, Intra-Household Sharing, Intra-Population Patterns, Cohabitation, Host Population Structures.Valles-Colomer, M., Blanco-Míguez, A., Manghi, P. et al. The person-to-person transmission landscape of the gut and oral microbiomes. Nature (2023). https://doi.org/10.1038/s41586-022-05620-1

In this episode, we're joined by Dr. Ognjen Ilic, a leading scientist in the field of acoustic waves and metasurfaces, to discuss how waves exert force on obstacles in their path and how this can be manipulated. Conventionally, the radiation force exerted by waves is limited by the shape and size of the objects being manipulated. Dr. Ilic, however, has made a breakthrough discovery that challenges this fundamental rule.Dr. Ilic explains how subwavelength-structured surfaces (metasurfaces) allow for the control of the radiation force exerted by acoustic waves, independent of the object's overall shape and size. The manipulation of this force is solely determined by the arrangement of the surface features on the metasurface.We delve into Dr. Ilic's fascinating experiments demonstrating how this anomalous metasurface scattering can enable complex actuation phenomena such as self-guidance and tractor beaming. In self-guidance, a metasurface object is autonomously guided by an acoustic wave, while in tractor beaming, a metasurface object is pulled by the wave.Join us as Dr. Ilic uncovers how the principles of metasurface acoustics can be applied to the domain of mechanical manipulation, ushering in new frontiers in contactless actuation and enabling diverse mechanisms that surpass the traditional limits of wave-matter interactions.Key Words: Metasurface Acoustics, Acoustic Waves, Radiation Force, Anomalous Metasurface Scattering, Self-Guidance, Tractor Beaming, Contactless Actuation.Stein, M., Keller, S., Luo, Y. et al. Shaping contactless radiation forces through anomalous acoustic scattering. Nat Commun 13, 6533 (2022). https://doi.org/10.1038/s41467-022-34207-7

In this episode, we welcome Dr. Kannan and his team, pioneers in neuroscience and the developers of Genetically Encoded Fluorescent Voltage Indicators (GEVIs). They share the intricate dynamics of signal processing in the brain, involving various excitatory and inhibitory neuron populations. Dr. Kannan's team discusses their innovations, including the second-generation GEVIs Ace-mNeon2 and VARNAM2. These have shown significantly improved voltage sensitivities and, along with their respective reverse response-polarity variants, provide an unparalleled suite of tools for multi-population voltage recordings in awake, behaving animals. The team also talks about their experiments involving these indicators, which allowed low-power recordings from a vast number of individual neurons in running mice. These investigations have unveiled fascinating insights into visual cortical cell type-specific responses to behavioral-state transitions. Their work has particularly highlighted the profound activation of cortical interneurons expressing somatostatin (SST) during a quiescence-to-arousal transition.Dr. Kannan and his team have explored the functional dynamics of pairs of neuron types and the contributions of distinct cell classes to the local field potential in the hippocampus. They discovered differences in the responses of neuron subclasses to state changes and even extracted the simultaneous real-time voltage dynamics of three neuron types. Join us in this episode as we delve into the insights gathered from the concerted dynamics of multiple cell classes in behaving animals. We also explore this technology's tremendous potential for furthering our understanding of brain function.Key Words: Neuroscience, Genetically Encoded Fluorescent Voltage Indicators, Brain Function, Neuron Populations, Ace-mNeon2, VARNAM2, Visual Cortical Cell, Local Field Potential.Dual-polarity voltage imaging of the concurrent dynamics of multiple neuron types https://doi.org/10.1126/science.abm8797

In this episode, we delve into the world of radiation biology with Dr. Siyao Wang. We explore the long-standing question of how paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring. This subject is of particular relevance considering that nearly 80% of transmitted mutations in humans arise from the paternal germline.Dr. Wang shares insights from her research using Caenorhabditis elegans strains, which reveal that paternal, not maternal, exposure to ionizing radiation leads to transgenerational embryonic lethality. The offspring of irradiated males display numerous genome instability phenotypes, such as DNA fragmentation, chromosomal rearrangement, and aneuploidy. Intriguingly, the repair process for paternal DNA double strand breaks involves maternally provided error-prone polymerase theta-mediated end joining.We further discuss the mechanisms that drive these outcomes, focusing on the roles of an orthologue of human histone H1.0, HIS-24, and the heterochromatin protein HPL-1. Dr. Wang elucidates how the depletion of these proteins can significantly reverse transgenerational embryonic lethality. She explains that the removal of HIS-24 or HPL-1 reduces histone 3 lysine 9 dimethylation and enables error-free homologous recombination repair in the germline of the F1 generation from ionizing radiation-treated P0 males, leading to improved viability of the F2 generation.Tune into this episode to gain a deeper understanding of the heritable consequences of paternal radiation exposure, an area of research that could shed light on congenital disorders and cancer in humans.Key Words: Radiation Biology, Paternal Radiation Exposure, Genetic Inheritance, Disease Risk, Transgenerational Embryonic Lethality, Genome Instability, DNA Fragmentation, Chromosomal Rearrangement, Aneuploidy, Homologous Recombination Repair, Histone H1.0, HIS-24, HPL-1.Wang, S., Meyer, D.H. & Schumacher, B. Inheritance of paternal DNA damage by histone-mediated repair restriction. Nature (2022). https://doi.org/10.1038/s41586-022-05544-w

In this episode, we speak with Dr. Stoeger about one of the most profound phenomena in biology—aging. As a critical factor influencing morbidity and mortality, understanding the molecular mechanisms behind aging is of paramount importance.Dr. Stoeger's research presents an intriguing perspective on this issue, revealing a strong relationship between transcript length and the transcriptional changes seen in aging in both mice and humans. It appears that as organisms age, there's a relative decrease in the abundance of long transcripts.We delve into three compelling pieces of evidence that underscore the biological significance of this discovery. Firstly, this association of transcript length with aging is prevalent in vertebrates. Secondly, various anti-aging interventions have been shown to counter this length association, pointing to possible therapeutic avenues. Lastly, we learn about an intriguing enrichment pattern—genes with the longest transcripts are linked to lifespan extension, while those with the shortest transcripts are often associated with a shortened lifespan.Join us as we unravel the secrets of aging and explore the complex organization of transcriptomes. It's an intriguing journey into the world of aging biology that you won't want to miss!Key Words: Aging, Transcriptome, Transcript Length, Lifespan, Anti-Aging Interventions, Genes, Mice, Humans, Long Transcripts, Short Transcripts.Stoeger, T., et al. Aging is associated with a systemic length-associated transcriptome imbalance. Nat Aging 2, 1191–1206 (2022). https://doi.org/10.1038/s43587-022-00317-6

In this episode, we sit down with Dr. Taverna to delve into the mysterious world of magnetars—neutron stars with ultra-strong magnetic fields. While magnetars are primarily observed at x-ray wavelengths, the precise mechanisms and geometry of the emitting regions have remained a puzzle.Dr. Taverna discusses their ground-breaking research that has taken a novel approach to studying these celestial bodies: measuring the x-ray polarization of the magnetar 4U 0142+61. These measurements revealed a fascinating and complex picture. The polarization degree and angle both change as a function of x-ray energy, pointing towards two distinct emission regions.The conversation dives into the preferred model where most of the x-rays are emitted by an equatorial band on the neutron star's surface. Some photons then undergo scattering to higher energies due to collisions with electrons in the surrounding magnetic field. This reprocessing of thermal radiation provides new insights into the properties of the magnetar's magnetic fields and surface.Join us as we uncover the secrets of magnetar emissions, guided by the intriguing insights drawn from x-ray polarization. It's an astronomical journey you don't want to miss!Key Words: Magnetars, Neutron Stars, X-ray Polarization, Emission Regions, Magnetic Fields, Scattering, 4U 0142+61, Equatorial Band, Charged Particles, Magnetosphere.https://doi.org/10.1126/science.add0080

In this enlightening episode, we engage in an in-depth conversation with Dr. Xu about his recent groundbreaking work on the quantization of linearly polarized photons from the Lorentz-boosted electromagnetic field of a nucleus traveling at ultrarelativistic speed.Dr. Xu's experiment investigates a fascinating scenario where two relativistic heavy nuclei pass each other at a distance of a few nuclear radii. The photon from one nucleus can interact with the gluons of the other through a virtual quark-antiquark pair, forming a short-lived vector meson, such as ρ0. This process, termed diffractive photoproduction, is used to observe a unique spin interference pattern in the angular distribution of ρ0 → π+π− decays.In an intriguing display of quantum mechanics, the observed interference results from the overlap of two wave functions at a distance that's an order of magnitude larger than the travel distance of the ρ0 within its lifetime. From these diffractive interactions, Dr. Xu and his team extracted the strong-interaction nuclear radii of 197Au and 238U, which were found to be larger than the nuclear charge radii.Join us as we delve into the quantum realm to understand how this observable can shed light on nuclear geometry and the quantum interference of nonidentical particles. It's an episode filled with profound insights about the fundamental nature of matter and forces!Key Words: Linearly Polarized Photon, Lorentz-Boosted Electromagnetic Field, Nuclear Radii, Quantum Interference, Diffractive Photoproduction, Spin Interference, Nuclear Geometry.Tomography of ultrarelativistic nuclei with polarized photon-gluon collisions https://doi.org/10.1126/sciadv.abq3903

In this enlightening episode, we chat with Dr. Elinav about his fascinating research on the association of certain gut microbes with inflammatory bowel diseases (IBD) and the potential use of phage therapy to combat these conditions. Dr. Elinav's work focuses on a clade of Klebsiella pneumoniae (Kp) strains, found to be associated with the severity and exacerbation of IBD in four distinct geographical cohorts. These strains, unique in their antibiotics resistance and mobilome signature, were observed to enhance intestinal inflammation when transferred into colitis-prone, germ-free, and colonized mice.Exploring the potential of phage therapy, Dr. Elinav and his team have designed a lytic five-phage combination that targets both sensitive and resistant members of the IBD-associated Kp clade, and effectively suppresses Kp in colitis-prone mice, leading to decreased inflammation and disease severity.Our conversation also covers the proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers, demonstrating the resilience, safety, and viability of these phages in the lower gut.Join us as we delve into the promise of phage therapy for managing gut microbes contributing to non-communicable diseases, a new frontier in IBD treatment.Key Words: Inflammatory Bowel Diseases, Klebsiella pneumoniae, Phage Therapy, Gut Microbiota, Pathobionts, Antibiotic Resistance, Non-Communicable Diseases.Dr. Elinav et al.: Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation https://doi.org/10.1016/j.cell.2022.07.003

In this intriguing episode, we have a conversation with Dr. Ari Benjamin, focusing on the parallels between human sensory systems and artificial neural networks in terms of their sensitivity to common features in the environment. Human sensory systems are notably more sensitive to common environmental features, and Dr. Benjamin's research reveals that artificial neural networks trained in object recognition demonstrate similar sensitivity patterns aligned with the statistics of image features. Dr. Benjamin explains a mathematical interpretation of these findings, showing that learning with gradient descent in neural networks preferentially forms representations that are more sensitive to common features, a characteristic of efficient coding. This effect appears in systems with otherwise unconstrained coding resources and occurs when learning towards both supervised and unsupervised objectives.Through our discussion, we delve into the notion that efficient codes can naturally emerge from gradient-like learning, highlighting the connections between human perception and AI learning mechanisms.Key Words: Artificial Intelligence, Sensory Perception, Gradient Descent, Neural Networks, Efficient Coding, Object Recognition, Supervised Learning, Unsupervised Learning.Benjamin, A.S., Zhang, LQ., Qiu, C. et al. Efficient neural codes naturally emerge through gradient descent learning. Nat Commun 13, 7972 (2022). https://doi.org/10.1038/s41467-022-35659-7

In this episode, we're joined by Dr. Rai, who enlightens us about the exciting field of precision protein engineering and its potential applications.Precision engineering of native proteins is akin to maintaining machinery – both necessitate an operational understanding and a robust set of tools for repair. Dr. Rai presents a technology that offers substantial control over various aspects of protein manipulation, including reactivity, chemoselectivity, site-selectivity, modularity, dual-probe installation, and protein-selectivity. This technology is known as cysteine-based chemoselective Linchpin-Directed site-selective Modification of lysine residue in a protein (LDMC-K).The strength of this user-friendly protocol lies in its ability to achieve quantitative conversions within an hour, leveraging chemically orthogonal C-S bond-formation and bond-dissociation. Interestingly, it offers the capacity to target a single lysine residue of a single protein in a complex biomolecular mixture, yielding an analytically pure single-site probe-engineered protein bioconjugate.The LDMC-K technique also enables the creation of homogeneous antibody conjugates, which demonstrate highly selective anti-proliferative activity towards breast cancer cells. Join us as we explore the depths of precision protein engineering, its implications, and its future prospects.Key Words: Precision Protein Engineering, LDMC-K, Reactivity, Chemoselectivity, Site-selectivity, Protein-selectivity, Breast Cancer, Antibody Conjugates.Reddy, N.C., Molla, R., Joshi, P.N. et al. Traceless cysteine-linchpin enables precision engineering of lysine in native proteins. Nat Commun (2022). https://doi.org/10.1038/s41467-022-33772-1

This episode features Dr. Kole, who shares fascinating insights into the world of myelination in parvalbumin-expressing (PV+) basket cells, a type of fast-spiking inhibitory interneurons vital for regulating local circuit activity and oscillations.PV+ axons are often myelinated, but the electrical and metabolic implications of interneuron myelination remain an open question in neuroscience. To delve deeper into this, Dr. Kole and his team developed viral constructs for cell type-specific investigation of mitochondria using genetically encoded fluorescent probes.Their investigations revealed a selective clustering of mitochondria to myelinated segments of PV+ basket cells. Interestingly, while the mitochondrial density increases in excitatory axons, cuprizone-induced demyelination erased mitochondrial clustering in PV+ axons. When the myelin basic protein was genetically deleted, they still observed mitochondrial clustering at internodes wrapped by noncompacted myelin, signifying that myelin compaction is not mandatory for this process.In the final part of their study, two-photon imaging was used to monitor action potential-evoked calcium (Ca2+) responses, which revealed that interneuron myelination reduces both the cytosolic and mitochondrial Ca2+ transients.These findings propose a unique role of oligodendrocyte ensheathment of PV+ axons in assembling mitochondria to selectively fine-tune metabolic demands. Join us as we uncover the mysteries of interneuron myelination with Dr. Kole.Key Words: Parvalbumin-expressing Basket Cells, Myelination, Mitochondrial Clustering, Cuprizone-induced Demyelination, Two-photon Imaging, Calcium Transients, Oligodendrocyte Ensheathment.Kole, K., et al. Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes. Nat Commun 13, 7598 (2022). https://doi.org/10.1038/s41467-022-35350-x

This episode features Dr. McWilliam, who discusses the intricate microbial immune-detection system in mammals revolving around MR1, a highly conserved protein. MR1 plays a crucial role in capturing vitamin B-related metabolite antigens from various microbes and displaying them at the cell surface to stimulate MR1-restricted lymphocytes, including mucosal-associated invariant T (MAIT) cells.This process of MR1 presentation and MAIT cell recognition aids in maintaining homeostasis through host defense and tissue repair mechanisms. However, the cellular mechanisms that regulate MR1 cell surface expression, which are critical for its function and MAIT cell recognition, remain largely unexplored.Dr. McWilliam and his team report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that facilitates low-affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction regulates the rate of MR1 internalization from the cell surface and restricts recycling.They propose that MR1 utilizes AP2 endocytosis to determine the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system. Join us in this episode to delve deeper into the exciting world of MR1 and MAIT cells with Dr. McWilliam.Key Words: MR1, Microbial Immune-Detection, Mucosal-Associated Invariant T Cells, Endocytic Adaptor Protein 2, Antigen Presentation, Host Defense.McWilliam et al. A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells. doi: 10.1083/jcb.202110125. Epub 2022 Sep 21. PMID: 36129434; PMCID: PMC9499830.

In this episode, Dr. Luque delves into the fascinating realm of exoplanets and their composition. With the majority of known temperate exoplanets orbiting red dwarf stars, these celestial bodies present an intriguing field for exploration and research.Dr. Luque and his colleague Pallé have been analyzing the masses and radii of these small transiting planets. Their research reveals three distinct populations - rocky, water-rich, and gas-rich. Contrary to the previously accepted bimodal radius distribution theory, which suggested atmospheric loss of a hydrogen/helium envelope, Dr. Luque proposes a new interpretation.Their findings suggest a density gap that separates rocky exoplanets from water-rich ones. This division could shed light on the planets' formation, possibly linked to their location within their planetary systems before orbital migration. According to their model, rocky planets form within the snow line, while water-rich planets form outside it and later migrate inward.Join us for an in-depth discussion with Dr. Luque as we delve into the intricacies of exoplanets, their formation, and the implications for our understanding of the universe.Key Words: Exoplanets, Red Dwarf Stars, Planet Composition, Planet Formation, Orbital Migration, Density Gap.Density, not radius, separates rocky and water-rich small planets orbiting M dwarf stars https://doi.org/10.1126/science.abl7164

DNA's mechanical and structural properties, dictated by local sequence and epigenetic modifications, have significant influence over a variety of DNA-deforming processes. However, comprehending this 'mechanical code' has been a complex task due to the lack of high-throughput experimental methods. Dr. Basu's research endeavors to unlock this intricate code.In this episode, we delve into Dr. Basu's groundbreaking research. Utilizing high-throughput measurements of DNA bendability through loop-seq, a technology developed by his team, Dr. Basu reveals how the occurrence and spatial distribution of dinucleotides, tetranucleotides, and methylated CpG influence DNA bendability.Building on these findings, Dr. Basu's team developed a physical model that captures the sequence and methylation dependence of DNA bendability. The model was further validated by using loop-seq on mouse genomic sequences around transcription start sites and CTCF-binding sites.The conversation also explores how the model was applied to test the predictions of all-atom molecular dynamics simulations and show that sequence and epigenetic modifications can mechanically encode regulatory information in various contexts.Join us as we traverse the fascinating terrain of DNA's mechanical code with Dr. Basu, opening up new avenues in our understanding of genetics and molecular biology.Key Words: DNA Bendability, Mechanical Code, Loop-seq, Dinucleotides, Tetranucleotides, Methylated CpG, All-atom Molecular Dynamics Simulations, Epigenetic Modifications.Basu, A., Bobrovnikov, D.G., Cieza, B. et al. Deciphering the mechanical code of the genome and epigenome. Nat Struct Mol Biol 29, 1178–1187 (2022). https://doi.org/10.1038/s41594-022--6

The three-dimensional folding of genes within the nuclear space is integral to understanding gene function and regulation, moving beyond the linear DNA sequence. Dr. Neguembor presents immuno-OligoSTORM, a revolutionary imaging strategy that super-resolves the distribution of nucleosomes within specific genes by simultaneously visualizing DNA and histones. In this episode, we dive into the technology behind immuno-OligoSTORM and how it integrates with restraint-based and coarse-grained modeling approaches to sync super-resolution imaging data with Hi-C contact frequencies and deconvoluted micrococcal nuclease-sequencing information. This results in Modeling immuno-OligoSTORM, a method that allows for quantitative modeling of genes with nucleosome resolution and reveals information about chromatin accessibility for regulatory factors, like RNA polymerase II.Join us as Dr. Neguembor elucidates how Modeling immuno-OligoSTORM allows exploration of intercellular variability, transcriptional-dependent gene conformation, and the folding of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells. This conversation promises to provide the highest degree of data integration on this subject so far.Key Words: immuno-OligoSTORM, Super-Resolution Imaging, Chromatin Architecture, DNA Folding, Nucleosomes, Restraint-based Modeling, Coarse-Grained Modeling, Hi-C Contact Frequencies, Micrococcal Nuclease-Sequencing, RNA Polymerase II.Neguembor, et al. MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution. Nat Struct Mol Biol 29, (2022). https://doi.org/10.1038/s41594-00839-y

Title: "Exploring Tumour Neo-Innervation and Anti-Tumour Immunity with Dr. Talbot"Description:The innervation of solid tumors by pain-initiating sensory neurons or nociceptors and its implications on cancer immunosurveillance is a subject of immense interest. In this episode, we're joined by Dr. Talbot, who discusses how melanoma cells interact with nociceptors, leading to their increased neurite outgrowth, sensitivity to noxious ligands, and neuropeptide release. Dr. Talbot delves into how Calcitonin Gene-Related Peptide (CGRP), a nociceptor-produced neuropeptide, can directly amplify the exhaustion of cytotoxic CD8+ T cells, limiting their ability to eliminate melanoma. Strategies like the genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors, and antagonism of the CGRP receptor RAMP1 all showed promising results in reducing leukocyte exhaustion and tumor growth, significantly increasing the survival rate of melanoma-bearing mice.Further, the conversation shifts to a critical finding: the reversal of CD8+ T cell exhaustion in sensory-neuron-depleted mice treated with local recombinant CGRP. Single-cell RNA sequencing of biopsies from melanoma patients further reveals the link between RAMP1-expressing CD8+ T cells and exhaustion, with RAMP1 overexpression correlating to a poorer prognosis. Join us as Dr. Talbot proposes a novel approach to improve anti-tumour immunity: curtailing the release of CGRP from tumor-innervating nociceptors to negate the immunomodulatory effects on cytotoxic CD8+ T cells.Key Words: Solid Tumours, Nociceptor Neurons, Cancer Immunosurveillance, Melanoma, Calcitonin Gene-Related Peptide (CGRP), CD8+ T Cells, TRPV1 Lineage, RAMP1, Anti-Tumour Immunity.Balood, M., Ahmadi, M., Eichwald, T. et al. Nociceptor neurons affect cancer immunosurveillance. Nature 611, 405–412 (2022). https://doi.org/10.1038/s41586-022-05374-w

The long childhood characteristic of our species is hypothesized to have evolved for learning complex foraging skills. This episode features Dr. Ilaria Pretelli, who investigates the connection between the development of foraging proficiency and the complexity of the foraging niche. Using published records of child and adolescent foragers from 28 different societies, Dr. Pretelli explores how skill-intensive different resources are and assess whether children’s proficiency increases more slowly for these resources.The discussion reveals that foraging returns for more skill-intensive and difficult-to-extract resources like tubers and game increase slowly, with peak productivity reached only in adulthood. In contrast, returns for easier-to-extract resources like fruit and fish/shellfish increase rapidly during childhood, achieving adult levels of productivity by adolescence. Dr. Pretelli's findings support the hypothesis that long childhoods evolved to allow extended periods for learning to extract complex resources characteristic of the human foraging niche. Join us in this episode as we delve into the intricate relationship between human development and the acquisition of crucial survival skills.Key Words: Human Development, Foraging Skills, Childhood Learning, Niche Complexity, Skill-intensive Resources, Foraging Returns, Evolution.Foraging complexity and the evolution of childhood https://doi.org/10.1126/sciadv.abn9889

In this enlightening episode, we delve into the realm of integrating neurons into digital systems with Dr. Kagan. Dr. Kagan presents his innovative development, DishBrain, which uses in vitro neural networks from human or rodent origins, integrated with in silico computing through a high-density multielectrode array. This fusion of biology and technology represents a significant leap towards creating synthetic biological intelligence.By embedding these cultures in a simulated game world, mimicking the arcade game "Pong," Dr. Kagan and his team observe learning within five minutes of real-time gameplay that is not seen in control conditions. The research demonstrates the importance of closed-loop structured feedback in eliciting learning over time.Dr. Kagan explains that these neural networks display the ability to self-organize activity in a goal-directed manner, responding to sparse sensory information about the consequences of their actions. This exploration of what the team has termed synthetic biological intelligence might offer valuable insights into the cellular correlates of intelligence, and it has the potential to revolutionize our understanding of both biological and artificial intelligence.Key Words: Synthetic Biological Intelligence, Neuron Integration, Digital Systems, DishBrain, In Vitro Neural Networks, In Silico Computing, Multielectrode Array, Active Inference, Free Energy Principle, Cellular Correlates of Intelligence.In vitro neurons learn and exhibit sentience when embodied in a simulated game world https://doi.org/10.1016/j.neuron.2022.09.001

In this compelling episode, Dr. Weijian Yang introduces us to a breakthrough in computational imaging: a compact and learnable lensless 3D camera capable of real-time photorealistic imaging. This technological innovation holds great promise in revolutionizing how we capture and interpret our world.The device, developed by Dr. Yang and his team, replaces traditional bulky optics with customized thin optical masks, making it lightweight and portable. Contrary to existing lensless imaging methods that require extensive calibration and heavy computational resources, this lensless 3D camera overcomes these challenges. Dr. Yang discusses the custom design and fabrication of the optical phase mask, optimized for spatial frequency support and axial resolving ability.The team has developed a robust physics-aware deep learning model with an adversarial learning module that allows for real-time depth-resolved photorealistic reconstructions. The ability of this lensless imager to resolve depth and "see-through" opaque obstacles offers transformative potential across a range of computational imaging applications.Join us as we delve into the future of imaging technology and its implications for a variety of fields, from medical imaging to remote sensing and beyond.Key Words: Computational Imaging, Lensless 3D Camera, Real-Time Imaging, Photorealistic Reconstruction, Optical Phase Mask, Physics-Aware Deep Learning, Adversarial Learning, Depth Resolution, See-Through Imaging.Tian F, Yang W. Learned lensless 3D camera. Opt Express. 2022 Sep 12;30(19):34479-34496. doi: 10.1364/OE.465933. PMID: 36242459; PMCID: PMC9576281.

In this enlightening episode, Dr. Ceren Kabukcu takes us back to the Paleolithic era as she shares her groundbreaking research on hunter-gatherer diets. While the predominant narrative has focused on the consumption of animals, Dr. Kabukcu sheds light on the significant role plants, particularly those with bitter and astringent tastes, played in ancient cuisine.Her team conducted an in-depth analysis of carbonised macro-remains of processed plants from Franchthi Cave in the Aegean Basin and Shanidar Cave in the north-west Zagros Mountains. Through microscopic examination of these charred food remains, they discovered the use of pounded pulses as a common ingredient in cooked plant foods.In our discussion, we explore the implications of these findings in the broader context of regional archaeobotanical literature. Dr. Kabukcu argues that despite their unappealing flavors to the modern palate, bitter and astringent plants were key ingredients of Palaeolithic cuisines in South-west Asia and the Eastern Mediterranean. Join us for this fascinating exploration of our dietary past, a journey that reveals how our ancestors turned nature's pantry into diverse and nourishing meals.Key Words: Palaeolithic Diet, Hunter-Gatherer, Plant Foods, Archaeobotany, Franchthi Cave, Shanidar Cave, Pounded Pulses, Bitter and Astringent Plants, South-west Asia, Eastern Mediterranean.Kabukcu, C. (2022). Cooking in caves: Palaeolithic carbonised plant food remains from Franchthi and Shanidar. Antiquity, 1-17. doi:10.15184/aqy.2022.143

In this enlightening episode, we travel back in time to unravel the mysteries of ancient Greek astronomy with Dr. Victor Gysembergh, a leading expert on the subject. The focus of our conversation is the recently discovered evidence for Hipparchus’ lost Star Catalogue, a breakthrough made possible through advanced multispectral imaging and meticulous interpretation of a palimpsest manuscript.Dr. Gysembergh shares with us the significance of these findings, revealing that they represent the most authoritative evidence to date for Hipparchus' Star Catalogue. The discovery notably confirms that the Star Catalogue was originally composed in equatorial coordinates, a fact that profoundly influences our understanding of ancient astronomical practices.Moreover, Dr. Gysembergh explains how the evidence reveals that Ptolemy’s Star Catalogue was not entirely based on data from Hipparchus' work, challenging long-standing assumptions in the field of historical astronomy.Perhaps most fascinating, the numerical evidence suggests that Hipparchus' Star Catalogue may have been accurate within 1° of the real stellar coordinates, outperforming even Claudius Ptolemy's renowned work in precision.Join us on this celestial journey as we explore the groundbreaking discoveries and delve into the precision and ingenuity of ancient astronomy. Uncover the complex narratives of knowledge transmission and scientific advancement that continue to resonate today.Key Words: Hipparchus, Star Catalogue, Ancient Astronomy, Multispectral Imaging, Palimpsest Manuscript, Equatorial Coordinates, Ptolemy, Claudius Ptolemy, Greek Astronomy, Historical Astronomy.New evidence for Hipparchus’ Star Catalogue revealed by multispectral imaging https://doi.org/10.1177/00218286221128289

This episode delves into the fascinating world of host-associated microbiotas with renowned scientist Dr. Eisen. His groundbreaking research uncovers how microbiotas guide the trajectory of developmental programs and influence social behavior.Dr. Eisen's team discovered that the zebrafish microbiota is required for normal social behavior, revealing a molecular pathway that connects the microbiota, microglial remodeling of neural circuits, and social behavior. This exploration was conducted using the experimentally tractable model vertebrate, the zebrafish.We discuss in depth how the microbiota restrains neurite complexity and targets forebrain neurons necessary for normal social behavior. We also delve into how the microbiota is crucial for localizing forebrain microglia, brain-resident phagocytes that remodel neuronal arbors.Dr. Eisen's research indicates that the microbiota influences microglial molecular functions, promoting the expression of the complement signaling pathway and the synaptic remodeling factor c1q. He shares with us his intriguing finding that several distinct bacterial taxa are individually sufficient for normal microglial and neuronal phenotypes, suggesting that host neuroimmune development is sensitive to a feature common among many bacteria.In this illuminating conversation, we explore how understanding the connection between microbiota and social behavior can open up pathways for new interventions in multiple neurodevelopmental disorders. Join us as we navigate this complex and intriguing interplay between our microbiota and our brains.Key Words: Microbiota, Neurodevelopment, Social Behavior, Microglial Remodeling, Neural Circuits, Zebrafish, Neurite Complexity, Forebrain Neurons, Neuroimmune Development, Neurodevelopmental Disorders.Eisen et al. (2022) The microbiota promotes social behavior by modulating microglial remodeling of forebrain neurons. doi:10.1371/journal.pbio.3001838

In this fascinating episode, we dive into the world of insects with Dr. Emonet, an expert in sensory processing and behavior. We explore how insects like Drosophila melanogaster, commonly known as the fruit fly, utilize odor plumes to navigate complex and rapidly changing environments in their quest for food and mates. Odour plumes, Dr. Emonet explains, are volatile, multidimensional signals carried by turbulent airflows. Insects are capable of extracting and integrating several features of these odour signals, including their identity, intensity, and timing. They also incorporate other sensory inputs like mechanosensory and visual cues. However, the conventional model of insect odour navigation has largely centered around the wind providing the primary directional cue.Dr. Emonet challenges this model, revealing that Drosophila melanogaster also uses another directional cue—the direction of motion of odors. This information is gathered using temporal correlations in the odor signal between the insect's two antennae. The processes employed, he elaborates, are akin to those used in visual-direction sensing.With the help of high-resolution virtual-reality paradigms, simulations, theory, and experiments, Dr. Emonet illustrates how this odor-direction sensing plays a critical role in navigating naturalistic plumes. The odor motion holds valuable directional information that is absent from airflow alone, proving beneficial to both Drosophila and virtual agents.This episode provides a glimpse into the elegant mechanisms at play in the insect world and raises exciting possibilities for the development of olfactory robot navigation in uncertain environments.Key Words: Insect navigation, Odour plumes, Drosophila melanogaster, Sensory inputs, Visual-direction sensing, Mechanosensory cues, Olfactory robot navigation, Sensory processing, and behavior.Kadakia, N., Demir, M., Michaelis, B.T. et al. Odour motion sensing enhances navigation of complex plumes. Nature (2022). https://doi.org/10.1038/s41586-022-05423-4

In this fascinating episode, we're joined by Dr. Mizuno, an expert in microbiology and biodiversity, who shares his recent discovery of a unique multicellular bacterium.Dr. Mizuno and his team identified a bacterium, HS-3, from an underground stream, demonstrating an entirely new type of prokaryotic multicellularity. The bacterium self-organizes its filamentous cells into layer-structured colonies, exhibiting properties similar to a nematic liquid crystal.The research team observed that these colonies mature into a semi-closed sphere containing clusters of coccobacillus daughter cells. Interestingly, the release of these cells is selective and happens upon contact with water.This groundbreaking discovery challenges our understanding of bacterial multicellularity and indicates that a liquid-crystal status can support prokaryotic multicellular behavior. Dr. Mizuno further delves into the ecological context of this phenomenon. He hypothesizes that the cyclic exposure of these colonies to the cave's water flow might have driven the evolutionary transition from unicellular to multicellular life forms.The findings, while preliminary, have exciting implications for a wide range of scientific disciplines, including microbiology, evolutionary biology, geobiology, and biophysics. Join us for this fascinating conversation as we explore the ecological contexts that foster multicellularity and the intriguing world of bacterial life with Dr. Mizuno.Key Words: Multicellularity, Bacterial Life, Prokaryotes, Microbiology, Ecology, Evolution, Biophysics, Geobiology, HS-3 Bacterium, Liquid Crystal, Coccobacillus Daughter Cells.Kouhei Mizuno et al. (2022) Novel multicellular prokaryote discovered next to an underground stream eLife 11:e71920 https://doi.org/10.7554/eLife.71920

In this episode, we are thrilled to have Dr. Xie, a notable figure in the intersection of computational biology and personalized medicine. His groundbreaking work focuses on developing innovative machine-learning models to predict patient-specific responses to new compounds, a key aspect of personalized drug discovery and development.The main hurdle in this field is the scarcity of patient data, which makes training a generalized machine-learning model challenging. To overcome this, Dr. Xie and his team created the context-aware de-confounding autoencoder (CODE-AE). This model can extract intrinsic biological signals obscured by context-specific patterns and confounding factors.In the course of our conversation, Dr. Xie shares the results of extensive comparative studies, showing that CODE-AE not only alleviated the out-of-distribution problem for model generalization but also significantly improved the accuracy and robustness in predicting patient-specific clinical drug responses. These results were achieved purely from cell-line compound screens, demonstrating the effectiveness of CODE-AE.Using this approach, Dr. Xie's team screened 59 drugs for over 9,800 cancer patients. The results align well with existing clinical observations, underscoring the potential of CODE-AE in developing personalized therapies and identifying drug response biomarkers.This episode is a must-listen for those interested in personalized medicine, computational biology, machine learning, and the future of drug discovery and development. Join us as we delve into the fascinating world of personalized medicine with Dr. Xie.Key Words: Personalized Medicine, CODE-AE, Machine Learning, Drug Discovery, Drug Development, Computational Biology, Cell-Line Compound Screens, Drug Response Biomarkers, Cancer Treatment.Xie et al. A context-aware de-confounding autoencoder for robust prediction of personalized clinical drug response from cell-line compound screening Nat 2022 https://doi.org/10.1038/s42256-022-00541-0

In this riveting episode, we host Dr. Qiu, a distinguished researcher whose work focuses on understanding the unique developmental differentiation within ant colonies. Ant colonies, much like higher-level organisms, consist of specialized reproductive and non-reproductive individuals, a phenomenon Dr. Qiu compares to germ-soma segregation in bilateral Metazoa.Dr. Qiu and his team have assembled more than 1,400 whole-genome transcriptomes to reconstruct the individual developmental trajectories of two ant species, Monomorium pharaonis, and Acromyrmex echinatior. Through this, they have been able to predict caste phenotypes with impressive accuracy using genome-wide transcriptome profiling.In our conversation, Dr. Qiu explains their finding that caste differentiation in ants is increasingly canalized from early development onwards, particularly in germline individuals (gynes/queens). He delves into the vital role of the juvenile hormone signaling pathway in this process by regulating body mass divergence between castes.Furthermore, they have identified and quantified gene-specific canalization levels and uncovered that canalized genes with gyne/queen-biased expression are linked to ovary and wing functions. On the other hand, canalized genes with worker-biased expression were enriched in brain and behavioral functions.By suppressing Freja, a highly canalized gyne-biased ovary gene in gyne larvae, they also demonstrate that any disturbance in the developmental pathway induces non-adaptive intermediate phenotypes between gynes and workers.Join us as Dr. Qiu takes us on a genomic journey exploring the intricate and fascinating world of ant colonies. This episode is a must-listen for anyone interested in genomics, developmental biology, and the sophisticated world of insect social structure.Key Words: Ant colonies, Developmental Differentiation, Genomics, Transcriptomes, Germ-Soma Segregation, Juvenile Hormone Signaling, Caste Phenotypes, Canalization, Ant Behavior, Evolutionary Biology.Qiu, B., Dai, X., Li, P. et al. Canalized gene expression during development mediates caste differentiation in ants. Nat Ecol Evol 6, 1753–1765 (2022). https://doi.org/10.1038/s41559-022-01884-y

We are excited to welcome Dr. Ando, an expert in phylogenetic reconstruction and evolutionary biology, in this episode. Dr. Ando's intriguing work centers on Ribonucleotide Reductases (RNRs) - essential enzymes used by all free-living organisms and many viruses in the biosynthesis of DNA precursors.RNRs exhibit tremendous diversity in terms of primary sequence and cofactor requirements while retaining a conserved fold and a radical-based mechanism for nucleotide reduction. Dr. Ando and his team have pieced together the most extensive phylogeny of RNRs to date, including a whopping 6779 sequences that unite all extant classes of the RNR family.During our discussion, Dr. Ando shares fascinating insights into their discovery of a novel, phylogenetically distinct clade that they have dubbed 'clade Ø'. This clade is ancestral to the classes I and II RNRs, and is a significant addition to our understanding of RNR evolution.Through a combination of techniques, including small-angle X-ray scattering (SAXS), cryogenic-electron microscopy (cryo-EM), and AlphaFold2, the team delves into the structure of a member of clade Ø, presenting the most minimal RNR architecture known to date. Based on their thorough analyses, Dr. Ando puts forth an evolutionary model for the diversification in the RNR family and discusses how their phylogeny could serve as a roadmap for future studies.Join us for this engrossing episode as we explore the fascinating evolution of the RNR family with Dr. Ando. This episode is an enlightening journey for anyone interested in evolutionary biology, phylogenetic reconstruction, structural biology, and the mechanisms of life at the molecular level.Key Words: Ribonucleotide Reductases, Phylogeny, Evolutionary Biology, Structural Biology, AlphaFold2, Cryogenic-Electron Microscopy, Small-Angle X-ray Scattering, DNA Biosynthesis, Protein Family Evolution.Nozomi Ando et al. (2022) Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade eLife 11:e79790 https://doi.org/10.7554/eLife.79790

In this episode, we welcome Dr. Cohen, a pioneer in the fascinating world of microscopic robots. Dr. Cohen's work aims to revolutionize fields such as medicine and environmental remediation by developing autonomous robots on a microscopic scale. These tiny systems, guided by onboard complementary metal oxide semiconductor electronics, have the potential to significantly impact a broad range of industries.During our conversation, Dr. Cohen delves into the intricacies of integrating information systems with microactuators, a key challenge in the creation of microscopic robots. He explains his team's process, which successfully integrates electronics fabricated at commercial foundries with microactuators.Dr. Cohen shares exciting details about the autonomous, untethered robots they've built, which range from 100 to 250 micrometers in size. Powered by light, these robots can walk at speeds greater than 10 micrometers per second. Notably, they've also demonstrated a microscopic robot capable of responding to an optical command.Join us as Dr. Cohen unravels the future of microscopic robots, offering insights into their potential uses and the technological advances that made them possible. If you're interested in robotics, AI, nanotechnology, or the intersection of technology and healthcare, this episode is a must-listen.Key Words: Microscopic Robots, Autonomous Robots, Complementary Metal Oxide Semiconductor Electronics, Microactuators, Robotics, Nanotechnology, Medicine, Environmental Remediation, Light-Powered Robots.Microscopic robots with onboard digital control https://doi.org/10.1126/scirobotics.abq2296

In this episode, we are joined by the renowned scientist Dr. Jack Feldman, whose work on the complex neural control system of breathing has been groundbreaking. Breathing, though seemingly simple, is a rhythmically regulated behavior vital for life and has profound influences on our brain and body.Dr. Feldman delves into the intricacies of the breathing central pattern generator (bCPG), a complex system that not only regulates gas exchange but also coordinates breathing with various behaviors. He sheds light on the role of the preBötzinger complex (preBötC), a central element of the bCPG, that drives inspiratory rhythm through an intricate emergent mechanism.Our conversation takes us through the synchronization dynamics that underpin preBötC rhythmogenesis, granting the system robustness and lability. We discuss how these dynamics are influenced by inputs from all over the brain and generate rhythmic, patterned activity that is widely distributed.Join us as Dr. Feldman elucidates the fascinating link between breathing, emotion, and cognition, backed by an emerging body of research. His insights hold promising implications for understanding function and dysfunction in breathing, as well as in other neural circuits of mammals.Key Words: Breathing, Central Pattern Generator, preBötzinger Complex, Neural Control System, Rhythmic Motor Behavior, Neural Circuits, Emotion, Cognition.Breathing Rhythm and Pattern and Their Influence on Emotion https://doi.org/10.1146/annurev-neuro-090121-014424

In this episode, we're delighted to welcome Abbigail Elms, who has been studying some of the coolest white dwarf stars known to date. Abbigail shares insights into two fascinating celestial bodies, WD J2147−4035 and WD J1922+0233, which are ultra-cool, metal-polluted (DZ) white dwarfs with surprisingly low temperatures. We discuss the intriguing features of these stars, including their unusually blue or red colours, as well as the innovative microphysics techniques Abbigail and her team use to understand them. Abbigail also reveals the extreme age of these white dwarfs - with WD J2147−4035 reaching over 10 billion years - and how they offer valuable information about the age of the Galactic disc in the Milky Way. Tune in to learn about these pivotal celestial objects and their potential impact on our understanding of the universe.Ultra-cool white dwarfs, metal-polluted, WD J2147−4035, WD J1922+0233, microphysics, model atmosphere code, collision-induced absorption, Galactic kinematics, Gaia EDR3 astrometry, Galactic disc, spectroscopy, sodium, potassium, calcium, lithium, Zeeman splitting, accreted planetary crust debris, Milky Way.Abbigail K Elms Spectral analysis of ultra-cool white dwarfs polluted by planetary debris, https://doi.org/10.1093/mnras/stac2908

In this episode, we delve into the intricate world of animal memory and decision-making with our esteemed guest, Dr. Clint Sergi. He sheds light on his fascinating research involving the memory capacity of the West black widow spider. Through an innovative experiment, Dr. Sergi and his team triggered search behaviors in these spiders by removing their prey from different areas of their webs, effectively 'stealing' it. This allowed them to infer what information the spiders retained about their prey - such as relative size and location of capture within the web. Join us as we explore this interesting study and the broader implications it has for our understanding of animal ecology, evolution, and memory formation.Key Words: Animal memories, adaptive decision-making, black widow spiders, searching behavior, prey theft, search effort, the memory of prey, prey size, prey capture location, gum-footed lines, behavioral observations, animal ecology, animal evolution, memory formation. Black widow spiders (Latrodectus hesperus) remember prey capture location and size but only alter behavior for prey caught at particular sites Clint Sergi, et al. https://doi.org/10.1111/eth.13328

This episode takes us on a journey into the vast world of Earth's microbial life with our distinguished guest, Dr. Averill. Microbes, particularly soil fungi, play an instrumental role in driving essential processes across diverse ecosystems - from our own bodies to vast forests. However, the biodiversity of these microscopic powerhouses is increasingly under threat. Dr. Averill's groundbreaking work advocates for the conservation, restoration, and active incorporation of soil microbes into managed landscapes. By analyzing data from 80 experiments, his team showed that restoring native soil microbiomes could accelerate plant biomass production by an average of 64% across ecosystems. Such restoration not only boosts and stabilizes yields in agriculture and forestry but also plays a critical role in preserving microbial biodiversity. As we navigate the emerging markets of ecosystem microbiome engineering, it's crucial to avoid past mistakes and prevent the creation of microbial monocultures. Join us as we delve into this exciting field of research, which holds the potential to revolutionize ecosystem management and conservation.Key Words: Microbial life, biodiversity, microbiome, conservation, restoration, soil fungi, plant biomass, ecosystem management, agriculture, forestry, microbial biodiversity, ecosystem vulnerability, pathogens, extreme events, microbial monocultures, ecosystem microbiome engineering.Averill, C., Anthony, M.A., Baldrian, P. et al. Defending Earth’s terrestrial microbiome. Nat Microbiol (2022). https://doi.org/10.1038/s41564-022-01228-3

Join us in this fascinating episode with Dr. Hawn as we delve into the realm of psychopathology, biological aging, and mortality. Psychopathology is often linked to faster biological aging and premature death. Dr. Hawn and her team's pioneering research have sought to better understand these relationships. They have examined associations between broad dimensions of psychopathology, post-traumatic stress disorder (PTSD), and GrimAge, a DNA methylation biomarker indicative of mortality risk relative to age. The research has also focused on understanding the neurobiological correlates of GrimAge, including neurocognitive functioning, inflammation, neuropathology, metabolic disease, and cortical thickness. Their findings show that externalizing psychopathology significantly predicts GrimAge, while PTSD appears to be linked to GrimAge in younger but not older cohorts. Also, GrimAge is associated with a variety of neurobiological variables, including cognitive disinhibition, memory recall, cardiometabolic pathology, oxidative stress, astrocyte damage, inflammation, and immune function. Tune in as we unpack these intriguing findings, and how they might aid in early disease identification and treatment.Key Words: Psychopathology, biological aging, mortality risk, GrimAge, PTSD, neurobiological correlates, neurocognitive functioning, inflammation, neuropathology, metabolic disease, cortical thickness, cardiometabolic pathology, oxidative stress, astrocyte damage, immune functioning, emotion regulation, facial recognition, disease identification, disease treatment.Hawn, et al. For whom the bell tolls: psychopathological and neurobiological correlates of a DNA methylation index of time-to-death. Transl Psychiatry(2022). https://doi.org/10.1038/s41398-022-02164-w

In this enlightening episode, we sit down with Dr. Longo to explore the intriguing role of fasting-mimicking diet (FMD) cycles in reducing Alzheimer's Disease (AD) symptoms and cognitive decline. The FMD cycles have demonstrated considerable potential in decreasing various aging and disease risk factors. As discussed by Dr. Longo, recent studies reveal that these diet cycles can reduce cognitive decline and AD pathology in mouse models more effectively than protein restriction cycles. Furthermore, long-term FMD cycles have demonstrated significant potential in reducing hippocampal Aβ load and hyperphosphorylated tau, enhancing neural stem cell genesis, decreasing the number of microglia, and reducing the expression of neuroinflammatory genes, including NADPH oxidase (Nox2). The deletion of Nox2 in mice or treatment with an NADPH oxidase inhibitor also leads to improved cognition and reduced microglia activation. Preliminary clinical data suggest the feasibility and general safety of FMD cycles in a small group of AD patients. Join us as Dr. Longo takes us through these fascinating findings that indicate FMD cycles' potential to delay cognitive decline in AD models by reducing neuroinflammation and superoxide production in the brain.Key Words: Fasting-Mimicking Diet (FMD), Alzheimer's Disease, Cognitive Decline, Aging, Disease Risk Factors, Protein Restriction, Neuroinflammation, Superoxide Production, NADPH Oxidase, Neural Stem Cells, Microglia, Aβ Load, Hyperphosphorylated Tau.Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer’s models https://doi.org/10.1016/j.celrep.2022.111417

Join us in this episode as we engage with Dr. Budson in discussing the evolution and complex roles of consciousness and memory. There is often a mix-up between why consciousness developed and the additional roles it has adopted over continued evolution. Dr. Budson proposes that consciousness originally evolved as part of the episodic memory system, likely to enable the flexible combination and rearrangement of past events to plan for the future. Over time, consciousness has been co-opted to fulfill other non-memory-related functions such as problem-solving, abstract thinking, and language. This theory, Dr. Budson argues, aligns with several phenomena, like the slow speed and the retrospective nature of consciousness, that other theories struggle to explain. Understanding this could have profound implications for our comprehension of intentional action and consciousness in general. Furthermore, Dr. Budson suggests that the systems of episodic, sensory, working, and semantic memory should collectively be viewed as the conscious memory system since they jointly contribute to the phenomenon of consciousness. He also contends that every cortical region of the brain contributes to this conscious memory system. Tune in as we dissect these intriguing perspectives and their potential impact on our understanding of consciousness.Key Words: Consciousness, memory, episodic memory, evolution, flexible recombination of information, problem-solving, abstract thinking, language, intentional action, sensory memory, working memory, semantic memory, conscious memory system, cerebral cortex.Consciousness as a Memory System Budson, Andrew E. MD*, Richman, Kenneth A. PhD; Kensinger, Elizabeth A. PhD Cognitive and Behavioral Neurology: doi: 10.1097/WNN.0000000000000319

In this insightful episode, we delve into the complex realm of epigenetics with Dr. Kaneshiro, exploring how parental epigenomes can significantly influence offspring development and health. Utilizing the model organism, Caenorhabditis elegans, Dr. Kaneshiro elaborates on the role of sperm-inherited histone marking in shaping offspring gene expression. Remarkably, the absence of the repressive mark H3K27me3 from the sperm genome leads to up-regulation from sperm alleles in offspring somatic and germline tissues. The research reveals that tissue context determines which genes are prone to up-regulation. Intriguingly, the findings mirror those in mammalian cells, suggesting a conserved mechanism for chromatin-based regulation. Furthermore, Dr. Kaneshiro reveals that the sperm-inherited pattern of gene marking and gene up-regulation are transmitted to grandoffspring, indicating that H3K27me3 marking can act as a bona fide transgenerational epigenetic carrier in C. elegans. Join us for this fascinating journey into the world of transgenerational epigenetics.Key Words: Epigenetics, Offspring Development, Parental Epigenomes, Caenorhabditis Elegans, Sperm-Inherited Histone Marking, Gene Expression, H3K27me3, Somatic Tissues, Germline Tissues, Transgenerational Epigenetic Carrier, Up-regulation, Chromatin-Based Regulation.Sperm-inherited H3K27me3 epialleles are transmitted transgenerationally in cishttps://doi.org/10.1073/pnas.2209471119

Dr. Sudimac joins us in this episode to unravel the intriguing relationship between urban living, natural environments, and mental health. As city living is often associated with an increased risk for mental disorders such as anxiety, depression, and schizophrenia, understanding how exposure to different environments influences mental health is crucial. Dr. Sudimac presents an intervention study exploring the changes in stress-related brain regions resulting from a one-hour walk in an urban or natural environment. Interestingly, amygdala activation, known to be associated with stress, decreases after a walk in nature but remains stable after an urban walk. This suggests that nature walks can have salutogenic effects on stress-related brain regions, potentially acting as a preventive measure against mental strain and disease. As we navigate the rapid urbanization of our world, this knowledge may significantly impact urban planning, emphasizing the creation of more accessible green spaces to support the mental well-being of citizens.Key Words: Mental Health, Urban Environments, Natural Environments, Anxiety, Depression, Schizophrenia, Amygdala Activation, Stress-Related Brain Regions, Intervention Study, Salutogenic Effects, Urban Planning, Green Spaces.Sudimac, S., Sale, V. & Kühn, S. How nature nurtures: Amygdala activity decreases as the result of a one-hour walk in nature. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01720-6

In this captivating episode, Dr. Tarduno delves into the mysteries of Earth's inner core, its structure, and how it began to crystallize. Through the lens of paleomagnetism, we explore the evolution of Earth's magnetic field, deciphering changes in its strength and understanding how these shifts provide clues about the core's history. Dr. Tarduno presents intriguing findings from single crystal paleointensity studies of early Cambrian anorthosites, which reveal a rapid resurgence of the magnetic field following a period of ultralow field strength in the Ediacaran Era. This dramatic shift pinpoints the inner core nucleation to around 550 million years ago. Further thermal modeling based on this age suggests the inner core had grown to half its present size by approximately 450 million years ago. Delving deeper, we discuss how seismic anisotropy within the inner core might reflect the development of global deep mantle structures, leaving an indelible imprint on our planet. Join us as we journey to the center of the Earth and back.Key Words: Inner Core, Paleomagnetism, Earth's Magnetic Field, Core Crystallization, Anorthosites, Inner Core Nucleation, Thermal Modeling, Seismic Anisotropy, Deep Mantle Structure, Earth's Geodynamo, Ediacaran Period, Cambrian Period.Zhou, T., Tarduno, J.A., Nimmo, F. et al. Early Cambrian renewal of the geodynamo and the origin of inner core structure. Nat Commun 13, 4161 (2022). https://doi.org/10.1038/s41467-022-31677-7

Delve into the intriguing world of prebiotic chemistry with Dr. Krishnamurthy as we explore the origins of α-amino acids and the evolutionary shift from the Strecker reaction to modern biological pathways. We discuss how α-ketoacids, through the Bucherer–Bergs pathway, react with cyanide and ammonia to form corresponding α-amino acids, highlighting the prebiotic transformation of oxaloacetate to aspartate. This transformation enables the formation of dihydroorotate, mirroring the biochemical synthesis of orotate—a precursor to pyrimidine nucleobases. We also examine how glyoxylate forms both glycine and orotate and reacts with malonate and urea to produce aspartate and dihydroorotate. Our conversation extends to the previously demonstrated protometabolic analogues of the Krebs cycle, underscoring the possibility of a natural emergence of biological pathways from prebiotic chemistry. This insightful discussion with Dr. Krishnamurthy illuminates the seamless transition from the primordial world of chemistry to the complexity of contemporary metabolism.Key Words: Prebiotic Chemistry, α-Amino Acids, Strecker Reaction, Bucherer–Bergs Pathway, α-Ketoacids, Oxaloacetate, Aspartate, Dihydroorotate, Orotate, Pyrimidine Nucleobases, Glyoxylate, Glycine, Malonate, Urea, Protometabolic Analogues, Krebs Cycle, Metabolic Evolution.Pulletikurti et al. Prebiotic synthesis of α-amino acids and orotate from α-ketoacids potentiates transition to extant metabolic pathways. Nat. Chem. (2022). https://doi.org/10.1038/s41557-022-00999-w