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Yu, I.

Publications and source records attributed to Yu, I..

2 recordsLinked to original sources

Friend Request Accepted: Fundamental Features of Social Environments Determine Rate of Social Affiliation

Humans start new friendships and social connections throughout their lives and such relationships foster mental and physical well-being. While friendship initiation may depend on alignment of subtle and complex personal variables, here we investigated whether it also depends on basic features of social environments. This would be analogous to other fundamental behaviours like foraging which depend on basic features of the environment such as the density of opportunities and the likelihood of success. In a pre-registered online study (n=783), we found people were more likely to send friend requests as the density of friendship opportunities decreased and frequency of success increased. Further, we found task-related measures, like overall friend requests, were correlated with personality-related factors like social thriving and anhedonia. Next, in an ultra-high-field fMRI study (n=24), we found that both fundamental features of social environments - opportunity density and frequency of success - affected neural activity across a network of regions linked to foraging including dorsal raphe nucleus, substantia nigra, and anterior insula. Finally, in resting-state fMRI data (n=400), we showed that model predicted estimates of anhedonia were related to functional connectivity between components of the same network. Thus, humans consider the background statistics of an environment while making social decisions and these decisions are linked to activity in ancient subcortical circuits mediating the influence of environmental statistics on other aspects of behaviour. Moreover, individual differences in how environmental features influence social behaviour are associated with variation in personality and psychiatric traits, offering new insights into inter-individual variability in social functioning.

neuroscience↗

A Non-Canonical IRAK Signaling Pathway Triggered by DNA Damage

Interleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptor (TLR) and IL-1R signaling, with no reported roles outside of innate immunity. We find that vertebrate cells exposed to ionizing radiation (IR) sequentially activate IRAK4 and IRAK1 through a phosphorylation cascade mirroring that induced by TLR/IL-1R, resulting in a potent anti-apoptotic response. However, IR-induced IRAK1 activation does not require the receptors or the IRAK4/1 adaptor protein MyD88, and instead of remaining in the cytoplasm, the activated kinase is immediately transported to the nucleus via a conserved nuclear localization signal. We identify: double-strand DNA breaks (DSBs) as the biologic trigger for this pathway; the E3 ubiquitin ligase Pellino1 as the scaffold enabling IRAK4/1 activation in place of TLR/IL-1R-MyD88; and the pro-apoptotic PIDDosome (PIDD1-RAIDD-caspase-2) as a critical downstream target in the nucleus. The data delineate a non-canonical IRAK signaling pathway derived from, or ancestral to, TLR signaling. This DSB detection pathway, which is also activated by genotoxic chemotherapies, provides multiple actionable targets for overcoming tumor resistance to mainstay cancer treatments.

cell biology↗