Integrated Calendar

Despite enormous experimental investment in searches of particle darkmatter, certain well-motivated corners of parameter space remain to beelusive "blind spots" for direct detection. In my talk I will address two ofsuch exceptions: light particles that simply do not have enough kineticenergy to detect, and strongly-interacting particles that quickly thermalizeand also become sub-threshold for direct detection. I show that both blindspots can be probed through double collisions of Dark matter -- first withsome energetic Standard model particles (solar electrons, cosmic rays,particles in a beam, neutrons in nuclear reactors etc) that bring DM toenergies above thresholds followed by the scattering inside a detector. Thisway, I derive novel constraints on light dark matter, as well as stronglyinteractingdark matter models, using existing dark matter and neutrinoexperiments.

Materials that are constantly driven out of thermodynamic equilibrium, such as active and living systems, typically violate the Einstein relation. This may arise from active contributions to particle fluctuations which are unrelated to the dissipative resistance of the surrounding medium. In this talk I will show that in these cases the widely used relation between informatic entropy production and heat dissipation does not hold. Consequently, fluctuation relations for the mechanical work, such as the Jarzynski and Crooks theorems, are invalid. The breaking of the correspondence between informatic entropy production and heat dissipation will then be related to the departure from the fluctuation-dissipation theorem. I will finally propose a temperaturelike variable that restores the correspondence between information and thermodynamics and gives rise to a generalized second law of thermodynamics. The Clausius inequality, Carnot maximum efficiency theorem, and relation between the extractable work and the change of free energy are recovered as well.

Development as a Metabolic Regulator: How Molting Controls Cholesteryl Ester Metabolism in the Somatic Stem Cells of C. elegans Raj Rani1, Or Ben-Hemo1, Benjamin Trabelcy1, Agam Bar1, Hans-Joachim Knölker2, Yoram Gerchman1,3,4, and Amir Sapir1*1Department of Biology and the Environment, Faculty of Natural Sciences, University of Haifa, Oranim, Tivon, 36006 Israel2 Fakultät Chemie, Technische Universität Dresden, Bergstrasse 66, 01069 Dresden, Germany3Institute of Evolution, Faculty of Natural Sciences, University of Haifa, Haifa, Israel4Oranim Academic College, Kiryat Tivon, Israel The metabolism of steroids, such as cholesterol, is critical for mammalian physiology and human health, yet its function in invertebrates remains poorly understood. Using Caenorhabditis elegans, we constructed the first comprehensive homology-based enzymatic atlas of steroid metabolism in invertebrates, identifying 159 candidate genes. We performed a two-dimensional genetic and metabolic screen, knocking down the atlas genes under varying cholesterol conditions to identify those functioning in steroid metabolism. Among the screen hits, we focused on mboa-1, an ortholog of mammalian SOAT1/2 enzymes that synthesize cholesteryl esters from sterols and fatty acids. Surprisingly, mboa-1 knockdown and knockout disrupt hypodermis and cuticle integrity. Consistent with its predicted enzymatic function, bacterially expressed C. elegans MBOA-1 generates cholesteryl esters when supplemented with the steroid 4,3-cholesta and fatty acids. Moreover, 4,3-cholesta—but not steroid hormones—rescued the mboa-1 RNAi phenotype, suggesting a new branch of steroid metabolism in C. elegans. mboa-1 is expressed specifically in the somatic stem cells of C. elegans, the seam cells, which contribute to the hypodermis and cuticle. Expression begins in mid-embryogenesis, persists throughout larval development, but declines sharply in adults. Underscoring its role in cuticle dynamics, mboa-1 expression oscillates with the molting cycle and is regulated by lin-29–mediated heterochronic control during the larval-to-adult transition, a stage when seam cells terminally differentiate. Our functional studies in Clade IV and V nematodes, along with insect expression data, suggest that during evolution, mboa-1 regulation was rewired to support a structural role for cholesteryl esters in cuticle formation, diverging from their primarily metabolic functions in mammals and insects. Our findings reveal how, during evolution, steroid metabolism was repurposed for a novel function in nematodes through the mechanistic reconfiguring of developmental regulation and stem cell biology.