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Latest Research Trends (21 Nov 2024)

Memories are not only in the brain, new research finds

Journal: Nature Communications

Author: N. V. Kukushkin, R. E. Carney, T. Tabassum, T. J. Carew, USA

The massed-spaced effect is a hallmark feature of memory formation. We now demonstrate this effect in two separate non-neural, immortalized cell lines stably expressing a short-lived luciferase reporter controlled by a CREB-dependent promoter. We emulate training using repeated pulses of forskolin and/or phorbol ester, and, as a proxy for memory, measure luciferase expression at various points after training. Four spaced pulses of either agonist elicit stronger and more sustained luciferase expression than a single “massed” pulse. Spaced pulses also result in stronger and more sustained activation of molecular factors critical for memory formation, ERK and CREB, and inhibition of ERK or CREB blocks the massed-spaced effect. Our findings show that canonical features of memory do not necessarily depend on neural circuitry, but can be embedded in the dynamics of signaling cascades conserved across different cell types.

Labeling cell particles with barcodes

Journal: Nature Communications

Author: Koki Kunitake, JAPAN

Cell-to-cell communication through nanosized particles, working as messengers and carriers, can now be analyzed in a whole new way, thanks to a new method involving CRISPR gene-editing technology. The particles, known as small extracellular vesicles (sEVs), play an important role in the spread of disease and as potential drug carriers. The newly developed system, named CIBER, enables thousands of genes to be studied at once, by labeling sEVs with a kind of RNA ‘barcode.’ With this, researchers hope to find what factors are involved in sEV release from host cells. This will help advance our understanding of basic sEV biology and may aid in the development of new treatments for diseases, such as cancer.

Fat cells have a ‘memory’ of obesity — hinting at why it’s hard to keep weight off

Journal: Nature

Author: Laura C. Hinte, Switzerland

Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity1,2. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes3,4. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding. In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic ‘yo-yo’ effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes.

Cytosolic delivery of innate immune agonists

Journal: Trends in Immunology

Author: Ravi Bharadwa, USA

Although cytosolic innate immune receptors are crucial for defending against pathogens that invade the intracellular space, it is well established that these receptors sense numerous innate triggers even when provided exogenously by neighboring cells or experimental manipulation. The molecular mechanisms by which these innate agonists access essential cytosolic sensors have been the focus of much recent discovery and constitute promising targets for perturbing the propagation of inflammation. In cancer immunotherapy, selectively targeting these pathways in the tumor microenvironment might also have therapeutic potential that is worth exploring.

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