Science Advances最新文献

The formation of new social interactions is vital for social animals, but the underlying neural mechanisms remain poorly understood. We identified CeA^Npbwr1 neurons, a population in central amygdala expressing neuropeptide B/W receptor-1 (NPBWR1), that play a critical role in these interactions. CeA^Npbwr1 neurons were activated during encounters with unfamiliar, but not with familiar, mice. Manipulations of CeA^Npbwr1 neurons showed that their excitation is essential for maintaining physical interactions with novel conspecifics. Activation of CeA^Npbwr1 neurons alleviated social deficits induced by chronic social defeat stress, suggesting therapeutic potential. Conversely, overexpression of human NPBWR1 in CeA^Npbwr1 neurons reduced activity of these neurons and impaired social interactions with unfamiliar mice. This effect was absent in a polymorphic variant of the human NPBWR1 gene (404A>T). These findings highlight how CeA^Npbwr1 neurons promote social novelty seeking and reveal a complex interplay between NPBWR1 genetic variations and social behavior.

A recurring challenge in extracting energy from ambient motion is that devices must maintain high harvesting efficiency and a positive user experience when the interface is undergoing dynamic compression. We show that small amphiphiles can be used to tune friction, haptics, and triboelectric properties by assembling into specific conformations on the surfaces of materials. Molecules that form multiple slip planes under pressure, especially through π-π stacking, produce 80 to 90% lower friction than those that form disordered mesostructures. We propose a scaling framework for their friction reduction properties that accounts for adhesion and contact mechanics. Amphiphile-coated surfaces tend to resist wear and generate distinct tactile perception, with humans preferring more slippery materials. Separately, triboelectric output is enhanced through the use of amphiphiles with high electron affinity. Because device adoption is tied to both friction reduction and electron-withdrawing potential, molecules that self-organize into slippery planes under pressure represent a facile way to advance the development of haptic power harvesters at scale.

Deep brain stimulation technology enables the neural modulation with precise spatial control but requires permanent implantation of conduits. Here, we describe a photothermal wireless deep brain stimulation nanosystem capable of eliminating α-synuclein aggregates and restoring degenerated dopamine neurons in the substantia nigra to treat Parkinson's disease. This nanosystem (ATB NPs) consists of gold nanoshell, an antibody against the heat-sensitive transient receptor potential vanilloid family member 1 (TRPV1), and β-synuclein (β-syn) peptides with a near infrared-responsive linker. ATB NPs by stereotactic injection target dopamine neurons expressing TRPV1 receptors in the substantia nigra. Upon pulsed near-infrared irradiation, ATB NPs, serving as nanoantennae, convert the light into heat, leading to calcium ion influx, depolarization, and action potentials in dopamine neurons through TRPV1 receptors. Simultaneously, β-synuclein peptides released from ATB NPs cooperate with chaperone-mediated autophagy initiated by heat shock protein, HSC70, to effectively eliminate α-synuclein fibrils in neurons. These orchestrated actions restored pathological dopamine neurons and locomotor behaviors of Parkinson's disease.

Disulfide bonds are ubiquitous molecular motifs that influence the tertiary structure and biological functions of many proteins. Yet, it is well known that the disulfide bond is photolabile when exposed to ultraviolet C (UVC) radiation. The deep-UV-induced S─S bond fragmentation kinetics on very fast timescales are especially pivotal to fully understand the photostability and photodamage repair mechanisms in proteins. In 1,2-dithiane, the smallest saturated cyclic molecule that mimics biologically active species with S─S bonds, we investigate the photochemistry upon 200-nm excitation by femtosecond time-resolved x-ray scattering in the gas phase using an x-ray free electron laser. In the femtosecond time domain, we find a very fast reaction that generates molecular fragments with one and two sulfur atoms. On picosecond and nanosecond timescales, a complex network of reactions unfolds that, ultimately, completes the sulfur dissociation from the parent molecule.