Integrated Calendar

<p>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.</p>

<p>Development as a Metabolic Regulator: How Molting Controls Cholesteryl Ester Metabolism in the Somatic Stem Cells of <em>C. elegans</em></p><p>&nbsp;</p><p>Raj Rani1, Or Ben-Hemo1, Benjamin Trabelcy1, Agam Bar1, Hans-Joachim Knölker2, Yoram Gerchman1,3,4, and Amir Sapir1*</p><p>1Department of Biology and the Environment, Faculty of Natural Sciences, University of Haifa, Oranim, Tivon, 36006 Israel</p><p>2 Fakultät Chemie, Technische Universität Dresden, Bergstrasse 66, 01069 Dresden, Germany</p><p>3Institute of Evolution, Faculty of Natural Sciences, University of Haifa, Haifa, Israel</p><p>4Oranim Academic College, Kiryat Tivon, Israel</p><p>&nbsp;</p><p>The metabolism of steroids, such as cholesterol, is critical for mammalian physiology and human health, yet its function in invertebrates remains poorly understood. Using <em>Caenorhabditis elegans</em>, 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 <em>mboa-1</em>, an ortholog of mammalian SOAT1/2 enzymes that synthesize cholesteryl esters from sterols and fatty acids. Surprisingly, <em>mboa-1</em> knockdown and knockout disrupt hypodermis and cuticle integrity. Consistent with its predicted enzymatic function, bacterially expressed <em>C. elegans</em> 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 <em>mboa-1</em> RNAi phenotype, suggesting a new branch of steroid metabolism in <em>C. elegans</em>. <em>mboa-1</em> is expressed specifically in the somatic stem cells of <em>C. elegans</em>, 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, <em>mboa-1</em> expression oscillates with the molting cycle and is regulated by <em>lin-29</em>–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, <em>mboa-1</em> 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.</p>

<p>Traumatic brain injury to the cortex elicits the loss of neurons at the site of damage, but also evokes changes in the tissue environment of axon terminals that project to the site of injury from distal locations.&nbsp; We previously demonstrated that basal forebrain cholinergic neurons (BFCNs) undergo retrograde degeneration following cortical TBI that is mediated by the p75 neurotrophin receptor (p75NTR).&nbsp; We have investigated mechanisms governing p75NTR-mediated retrograde degeneration as well as the behavioral consequences of the loss of BFCNs following TBI. &nbsp;Mice lacking the p75NTR in cholinergic neurons showed sparing of these neurons following TBI, and preservation of cognitive function.</p>