Macrolides for chronic asthma.

Lower urinary tract dysfunction (LUTd) represents a major health care problem with a high, unmet medical need. Design of additional therapies for LUTd requires precise tools to study bladder storage and voiding (dys)function in animal models. We developed videocystometry in mice, combining intravesical pressure measurements with high-speed fluoroscopy of the urinary tract. Videocystometry substantially outperforms current state-of-the-art methods to monitor the urine storage and voiding process, by enabling quantitative analysis of voiding efficiency, urethral flow, vesicoureteral reflux, and the relation between intravesical pressure and flow, in both anesthetized and awake, nonrestrained mice. Using videocystometry, we identified localized bladder wall micromotions correlated with different states of the filling/voiding cycle, revealed an acute effect of TRPV1 channel activation on voiding efficiency, and pinpointed the effects of urethane anesthesia on urine storage and urethral flow. Videocystometry has broad applications, ranging from the elucidation of molecular mechanisms of bladder control to drug development for LUTd.The function of several G protein-coupled receptors (GPCRs) exhibits cholesterol sensitivity. Cholesterol sensitivity of GPCRs could be attributed to specific sequence and structural features, such as the cholesterol recognition/interaction amino acid consensus (CRAC) motif, that facilitate their cholesterol-receptor interaction. In this work, we explored the molecular basis of cholesterol sensitivity exhibited by the serotonin1A receptor, the most studied GPCR in the context of cholesterol sensitivity, by generating mutants of key residues in CRAC motifs in transmembrane helix 2 (TM2) and TM5 of the receptor. Our results show that a lysine residue (K101) in one of the CRAC motifs is crucial for sensing altered membrane cholesterol levels. Insights from all-atom molecular dynamics simulations showed that cholesterol-sensitive functional states of the serotonin1A receptor are associated with reduced conformational dynamics of extracellular loops of the receptor. These results constitute one of the first reports on the molecular mechanism underlying cholesterol sensitivity of GPCRs.We introduce a general mechanism for superconductivity in Fermi systems with strong repulsive interaction. Because kinetic terms are small compared to the bare repulsion, the dynamics of charge carriers is constrained by the presence of other nearby carriers. By treating kinetic terms as a perturbation around the atomic limit, we show that pairing can be induced by correlated multiparticle tunneling processes that favor two itinerant carriers to be close together. Our analytically controlled theory provides a quantitative formula relating Tc to microscopic parameters, with maximum Tc reaching about 10% of the Fermi temperature. Our work demonstrates a powerful method for studying strong coupling superconductivity with unconventional pairing symmetry. It also offers a realistic new route to realizing finite angular momentum superfluidity of spin-polarized fermions in optical lattice.The balance between exploiting known actions and exploring alternatives is critical for survival and hypothesized to rely on shifts in neuromodulation. We developed a behavioral paradigm to capture exploitative and exploratory states and imaged calcium dynamics in genetically identified dopaminergic and noradrenergic neurons. During exploitative states, characterized by motivated repetition of the same action choice, dopamine neurons in SNc encoding movement vigor showed sustained elevation of basal activity that lasted many seconds. This sustained activity emerged from longer positive responses, which accumulated during exploitative action-reward bouts, and hysteretic dynamics. Conversely, noradrenergic neurons in LC showed sustained inhibition of basal activity due to the accumulation of longer negative responses in LC. Chemogenetic manipulation of these sustained dynamics revealed that dopaminergic activity mediates action drive, whereas noradrenergic activity modulates choice diversity. These data uncover the emergence of sustained neural states in dopaminergic and noradrenergic networks that mediate dissociable aspects of exploitative bouts.Photoluminescence (PL) from excitons serves as a powerful tool to characterize the optoelectronic property and band structure of semiconductors, especially for atomically thin two-dimensional transition metal dichalcogenide (TMD) materials. However, PL quenches quickly when the thickness of TMD materials increases from monolayer to a few layers, due to the change from direct to indirect band transition. Here, we show that PL can be recovered by engineering multilayer heterostructures, with the band transition reserved to be a direct type. We report emission from layer-engineered interlayer excitons from these multilayer heterostructures. Moreover, as desired for valleytronics devices, the lifetime, valley polarization, and valley lifetime of the generated interlayer excitons can all be substantially improved as compared with that in the monolayer-monolayer heterostructure. this website Our results pave the way for controlling the properties of interlayer excitons by layer engineering.Nanoscale magnetic structures are fundamental to the design and fabrication of spintronic devices and have exhibited tremendous potential superior to the conventional semiconductor devices. However, most of the magnetic moments in nanostructures are unstable due to size effect, and the possible solution based on exchange coupling between nanomagnetism is still not clear. Here, graphene-mediated exchange coupling between nanomagnets is demonstrated by depositing discrete superparamagnetic Ni nano-islands on single-crystal graphene. The heterostructure exhibits ideal two-dimensional (2D) ferromagnetism with clear hysteresis loops and Curie temperature up to 80 K. The intrinsic ferromagnetism in graphene and antiferromagnetic exchange coupling between graphene and Ni nano-islands are revealed by x-ray magnetic circular dichroism and density functional theory calculations. The artificial 2D ferromagnets constitute a platform to study the coupling mechanism between complex correlated electronic systems and magnetism on the nanoscale, and the results and concept provide insights into the realization of spin manipulation in quantum computing.this website