Structural basis for UFM1 transfer from UBA5 to UFC1

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Atomic coordinates and structure factors were deposited in the RCSB PDB (https://www.rcsb.org/) with the accession codes 7NW1, 7NVK, and 7NVJ for UFC1-UBA5 (389–404), UBA5(347-404)-UFC1, and UFC1(Y110A and F121A), respectively. NMR assignments for UFC1 were taken from the BMRB entry 6546. Previously published crystal structures used in this study are available from the RCSB PDB under the accession codes: 3TGD; 1J7D; 1U9A; 1×23; 1Y6L; 4Q5E; 4YII; 1Y8X; 1WZW; 6CYO; 1FZY; 1YLA; 2YBF; 2C4P; 5LBN; 3FN1; 2CYX; 2Z5D; 2F4W; 5BNB; 1YH2; 1YRV; 2Z6P; 2Z6O; 1JBB; 4Q5H; 1WZV; 3RZ3; 2DYT; 6H77. The coordinates of the structural models generated by in silico docking are provided as Supplementary Data 1–3. Source data are provided with this paper.Ufmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present the crystal structure of UFC1 bound to the C-terminus of UBA5, revealing how UBA5 interacts with UFC1 via a short linear sequence, not observed in other E1-E2 complexes. We find that UBA5 has a region outside the adenylation domain that is dispensable for UFC1 binding but critical for UFM1 transfer. This region moves next to UFC1’s active site Cys and compensates for a missing loop in UFC1, which exists in other E2s and is needed for the transfer. Overall, our findings advance the understanding of UFM1’s conjugation machinery and may serve as a basis for the development of ufmylation inhibitors.Israel Science FoundationIsrael Cancer Research FundUS-Israel Binational Science Foundatio

Fractionalization and trust in India: A field-experiment

Is India's high fractionalization associated with mistrust between its two main religious communities? An inter-ethnic trust game field experiment confirms intergroup bias in mutually lower offers between urban Muslims and Hindus in Mumbai. There are no differences in trustworthiness based on the religion of responders or of the co-players they respond to. Hindus generally have greater trust and expectations of others' trust but also of ethnocentrism

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Reduced neural feedback signaling despite robust neuron and gamma auditory responses during human sleep.

During sleep, sensory stimuli rarely trigger a behavioral response or conscious perception. However, it remains unclear whether sleep inhibits specific aspects of sensory processing, such as feedforward or feedback signaling. Here, we presented auditory stimuli (for example, click-trains, words, music) during wakefulness and sleep in patients with epilepsy, while recording neuronal spiking, microwire local field potentials, intracranial electroencephalogram and polysomnography. Auditory stimuli induced robust and selective spiking and high-gamma (80-200 Hz) power responses across the lateral temporal lobe during both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Sleep only moderately attenuated response magnitudes, mainly affecting late responses beyond early auditory cortex and entrainment to rapid click-trains in NREM sleep. By contrast, auditory-induced alpha-beta (10-30 Hz) desynchronization (that is, decreased power), prevalent in wakefulness, was strongly reduced in sleep. Thus, extensive auditory responses persist during sleep whereas alpha-beta power decrease, likely reflecting neural feedback processes, is deficient. More broadly, our findings suggest that feedback signaling is key to conscious sensory processing

Book Reviews

The Intelligence Wars: Lessons from Baghdad by Steven K.O\u27Hern. Spies for Hire: The Secret World of Intelligence Outsourcing by Tim Shorrock. The Shadow Factory: The Ultra-Secret NSA from 9/11 to the Eavesdropping on America by James Bamford. Human Intelligence, Counterterrorism, and National Leadership: A Practical Guide by Gary Berntsen. Executive Measures, Terrorism, and National Security—Have the Rules of the Game Changed? by David Bonner. The Human Factor: Inside the CIA\u27s Dysfunctional Intelligence Culture by Ishmael Jones. The Lost Spy: An American in Stalin\u27s Secret Service by Andrew Meier. Threats to Homeland Security: An All-Hazards Perspective. Edited by Richard J. Kilroy, Jr