Promiscuous G-protein activation by the calcium-sensing receptor.

The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca2+ concentration and maintains Ca2+ homeostasis1,2. It also mediates diverse cellular processes not associated with Ca2+ balance3-5. The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes6. We determined structures of CaSR in complex with G proteins from three different subfamilies: Gq, Gi and Gs. We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Gα subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1-ICL3), an extended transmembrane helix 3 and an ordered C-terminal region. G-protein binding expands the transmembrane dimer interface, which is further stabilized by phospholipid. The restraint imposed by the receptor dimer, in combination with ICL2, enables G-protein activation by facilitating conformational transition of Gα. We identified a single Gα residue that determines Gq and Gs versus Gi selectivity. The length and flexibility of ICL2 allows CaSR to bind all three Gα subtypes, thereby conferring capacity for promiscuous G-protein coupling.

Gut-brain circuits for fat preference.

The perception of fat evokes strong appetitive and consummatory responses1. Here we show that fat stimuli can induce behavioural attraction even in the absence of a functional taste system2,3. We demonstrate that fat acts after ingestion via the gut-brain axis to drive preference for fat. Using single-cell data, we identified the vagal neurons responding to intestinal delivery of fat, and showed that genetic silencing of this gut-to-brain circuit abolished the development of fat preference. Next, we compared the gut-to-brain pathways driving preference for fat versus sugar4, and uncovered two parallel systems, one functioning as a general sensor of essential nutrients, responding to intestinal stimulation with sugar, fat and amino acids, whereas the other is activated only by fat stimuli. Finally, we engineered mice lacking candidate receptors to detect the presence of intestinal fat, and validated their role as the mediators of gut-to-brain fat-evoked responses. Together, these findings reveal distinct cells and receptors that use the gut-brain axis as a fundamental conduit for the development of fat preference.

Classification of Reservoirs and Fluids in Tight Sandstone Based on the NMR Logging Technique-A Case Study of the Upper Paleozoic in the Ordos Basin.

The Upper Paleozoic strata in the Ordos Basin are dominated by tight sandstone gas reservoirs characterized by strong heterogeneity and widely distributed aquifers. Laterally, there is no evidently continuous distribution of water and gas, and longitudinally, the gas and aquifers are mostly in isolated intersections without uniform gas-water contact, rendering difficulties for effectively identifying the reservoir and fluid properties by using traditional mud logging technology. To solve these problems mentioned, the reservoirs were classified by integrating the T2 spectra of cores obtained through nuclear magnetic resonance (NMR) logging, regional geological characteristics, and gas test results. It is indicated in the result that the "three-division" method can reflect the type of storage space, and the structural movement and sedimentary thickness in the basin are primary factors for the formation of reservoirs of various types. The "nine-division" method is closely related to characteristics of "initial tightening and subsequent accumulation" of the basin and the gas test results, which can give insights into natural gas charging status in the tight sandstone samples, thereby effectively identifying fluid properties.

Effect of Laser Quenching-Shock Peening Strengthening on the Microstructure and Mechanical Properties of Cr12MoV Steel.

The automobile covering parts mold is a key piece of equipment in the automobile industry, and its drawbead is the core element that affects the life of the mold and the quality of the parts made. Due to the complex structure of the mold cavity for covering parts, there exist differences between material flow characteristics, load conditions, stress strain, failure forms and so on in the surface of different parts of its drawbead and the different directions of the same part of the drawbead, thus putting forward new requirements for material strengthening. For the differentiated lose efficacy forms of the dangerous end faces of the tension bars, this study carried out research into the effect of laser quenching-shock peening strengthening (LQ-LSP) on the organization, plastic deformation resistance and wear resistance of Cr12MoV steel. It was shown that the microhardness (722.30 HV) and residual stress (-383.84 MPa) of the specimens were further enhanced after laser quenching-shock peening composite strengthening. The residual austenite content of the specimen was reduced to 0.8%, and the eutectic carbide distribution morphology was improved. After three rounds of laser composite peening, the specimens had the smallest displacement of the nanoindentation load-depth curve, which exhibited the greatest nanohardness (20.0 Pa) and modulus of elasticity (565.25 Pa), while reducing the coefficient of friction (0.61) and surface roughness (0.152 Ra). The smooth and flat surface of the specimen with shallow and narrow plow grooves improved the resistance of Cr12MoV steel to plastic deformation and wear.

BacFlash signals acid-resistance gene expression in bacteria.

Intracellular pH (pHi) homeostasis is crucial for cellular functions and signal transduction across all kingdoms of life. In particular, bacterial pHi homeostasis is important for physiology, ecology, and pathogenesis. Here we report an exquisite bacterial acid-resistance (AR) mechanism in which proton leak elicits a pre-emptive AR response. A single bacterial cell undergoes quantal electrochemical excitation, termed "BacFlash", which consists of membrane depolarization, transient pHi rise, and bursting production of reactive oxygen species. BacFlash ignition is dictated by acid stress in the form of proton leak across the plasma membrane and the rate of BacFlash occurrence is reversely correlated with the pHi buffering capacity. Through genome-wide screening, we further identify the ATP synthase Fo complex subunit a as the putative proton sensor for BacFlash biogenesis. Importantly, persistent BacFlash hyperactivity activates transcription of a panel of key AR genes and predisposes the cells to survive imminent extreme acid stress. These findings demonstrate a prototypical coupling between electrochemical excitation and nucleoid gene expression in prokaryotes.