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Nature Biotechnology, Published online: 08 May 2023; doi:10.1038/s41587-023-01747-2

A multimodal atlas of retinal organoid development shows spatial interactions over time.

Nature, Published online: 21 December 2021; doi:10.1038/d41586-021-03778-8

Upgrade the science and technology policy system the US already has

In Caenorhabditis elegans, ablation of germline stem cells (GSCs) extends lifespan, but also increases fat accumulation and alters lipid metabolism, raising the intriguing question of how these effects might be related. Here, we show that a lack of GSCs results in a broad transcriptional reprogramming in which the conserved detoxification regulator SKN-1/Nrf increases stress resistance, proteasome activity, and longevity. SKN-1 also activates diverse lipid metabolism genes and reduces fat storage, thereby alleviating the increased fat accumulation caused by GSC absence. Surprisingly, SKN-1 is activated by signals from this fat, which appears to derive from unconsumed yolk that was produced for reproduction. We conclude that SKN-1 plays a direct role in maintaining lipid homeostasis in which it is activated by lipids. This SKN-1 function may explain the importance of mammalian Nrf proteins in fatty liver disease and suggest that particular endogenous or dietary lipids might promote health through SKN-1/Nrf.

DOI: http://dx.doi.org/10.7554/eLife.07836.001

Publication date: 25 August 2016
Source:Cell, Volume 166, Issue 5
Author(s): Emilie Marcus

Publication date: 22 August 2016
Source:Current Biology, Volume 26, Issue 16
Author(s): Gioia De Franceschi, Tipok Vivattanasarn, Aman B. Saleem, Samuel G. Solomon
In prey species such as mice, avoidance of predators is key to survival and drives instinctual behaviors like freeze or flight [1, 2]. Sensory signals guide the selection of appropriate behavior [3], and for aerial predators only vision provides useful information. Surprisingly, there is no evidence that vision can guide the selection of escape strategies. Fleeing behavior can be readily triggered by a rapidly looming overhead stimulus [4]. Freezing behavior, however, has previously been induced by real predators or their odors [5]. Here, we discover that a small moving disk, simulating the sweep of a predator cruising overhead, is sufficient to induce freezing response in mice. Looming and sweeping therefore provide visual triggers for opposing flight and freeze behaviors and provide evidence that mice innately make behavioral choices based on vision alone. Video Abstract

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De Franceschi et al. discover that the visual simulation of a predator cruising overhead induces freezing responses in mice. Visual simulation of a rapidly approaching predator instead induces flight responses. These findings provide evidence that mice innately make behavioral choices based on vision alone.

Publication date: 14 July 2016
Source:Cell, Volume 166, Issue 2
Author(s): Orane Guillaume-Gentil, Rashel V. Grindberg, Romain Kooger, Livie Dorwling-Carter, Vincent Martinez, Dario Ossola, Martin Pilhofer, Tomaso Zambelli, Julia A. Vorholt
Because of cellular heterogeneity, the analysis of endogenous molecules from single cells is of significant interest and has major implications. While micromanipulation or cell sorting followed by cell lysis is already used for subsequent molecular examinations, approaches to directly extract the content of living cells remain a challenging but promising alternative to achieving non-destructive sampling and cell-context preservation. Here, we demonstrate the quantitative extraction from single cells with spatiotemporal control using fluidic force microscopy. We further present a comprehensive analysis of the soluble molecules withdrawn from the cytoplasm or the nucleus, including the detection of enzyme activities and transcript abundances. This approach has uncovered the ability of cells to withstand extraction of up to several picoliters and opens opportunities to study cellular dynamics and cell-cell communication under physiological conditions at the single-cell level.

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Extraction of sub-picoliter samples of nucleoplasm and cytoplasm from live cells allows cellular heterogeneity to be assessed without killing the cells.

Publication date: 9 August 2016
Source:Cell Metabolism, Volume 24, Issue 2
Author(s): Hyo Youl Moon, Andreas Becke, David Berron, Benjamin Becker, Nirnath Sah, Galit Benoni, Emma Janke, Susan T. Lubejko, Nigel H. Greig, Julie A. Mattison, Emrah Duzel, Henriette van Praag
Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition.

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Moon et al. show that cathepsin B (CTSB), an exercise myokine, has beneficial effects on cognition such as enhanced adult hippocampal neurogenesis and spatial memory in mice. Treadmill exercise elevated plasma CTSB in monkeys and humans. In humans, CTSB levels correlated with fitness and hippocampus-dependent memory function.

by Julia Jaroslawska, Agnieszka Chabowska-Kita, Monika M. Kaczmarek, Leslie P. Kozak

Publication date: 18 June 2015
Source:Cell, Volume 161, Issue 7
Author(s): Jacob A. Berry , Isaac Cervantes-Sandoval , Molee Chakraborty , Ronald L. Davis
Early studies from psychology suggest that sleep facilitates memory retention by stopping ongoing retroactive interference caused by mental activity or external sensory stimuli. Neuroscience research with animal models, on the other hand, suggests that sleep facilitates retention by enhancing memory consolidation. Recently, in Drosophila, the ongoing activity of specific dopamine neurons was shown to regulate the forgetting of olfactory memories. Here, we show this ongoing dopaminergic activity is modulated with behavioral state, increasing robustly with locomotor activity and decreasing with rest. Increasing sleep-drive, with either the sleep-promoting agent Gaboxadol or by genetic stimulation of the neural circuit for sleep, decreases ongoing dopaminergic activity, while enhancing memory retention. Conversely, increasing arousal stimulates ongoing dopaminergic activity and accelerates dopaminergic-based forgetting. Therefore, forgetting is regulated by the behavioral state modulation of dopaminergic-based plasticity. Our findings integrate psychological and neuroscience research on sleep and forgetting.

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Sleep is generally thought to stabilize new memories, but early psychology studies suggest that it prevents new learning from interfering with old memories. This study shows that sleep suppresses the activity of dopamine neurons that promote active forgetting of olfactory memories in flies, providing integration between neuroscience and psychology research.