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GPRC6A, a member of the Family C G‐protein coupled receptors, regulates energy metabolism and sex hormone production and is activated by diverse ligands, including cations, L‐amino acids, the osteocalcin (Ocn) peptide and the steroid hormone testosterone. We sought a structural framework for the ability of multiple distinct classes of ligands to active GPRC6A. We created a structural model of GPRC6A using Alphafold2. Using this model we explored a putative orthosteric ligand binding site in the bilobed Venus fly trap (VFT) domain of GPRC6A and two positive allosteric modulator (PAM) sites, one in the VFT and the other in the 7 transmembrane (7TM) domain. We provide evidence that Ocn peptides act as a PAM for GPRC6A by binding to a site in the VFT that is distinct from the orthosteric site for calcium and L‐amino acids. In agreement with this prediction, alternatively spliced GPRC6A isoforms 2 and 3, which lack regions of the VFT, and mutations in the computationally predicted Ocn binding site, K352E and H355P, prevent Ocn activation of GPRC6A. These observations explain how dissimilar ligands activate GPRC6A and set the stage to develop novel molecules to activate and inhibit this previously poorly understood receptor. [ABSTRACT FROM AUTHOR]

Based on the deoxyribonucleic acid (DNA) sequence operations and chaotic systems, a novel improved color image encryption algorithm is presented with one-time-pad. Three DNA matrices are obtained by DNA encoding the plain-image firstly. To enhance the proposed algorithm's robustness of resisting known-plaintext and chosen-plaintext attacks, the key streams, which are used to scramble the positions of the three DNA matrices, are generated from 3D skew tent map (3D-STM) by using the secret keys and the hamming distances between the DNA matrices. Then, we perform the DNA XOR, addition and subtraction operations on the DNA matrices and the key streams to get the cipher-image. At this stage, we also update the initial values of the coupled map lattice (CML) by the circle distance of DNA matrices obtained from the previous step to further enhance the proposed algorithm's ability of resisting plaintext attack. Finally, we get the encrypted color image by decoding DNA matrices. The simulation and security analysis show that the proposed algorithm has an extraordinary ability to resist plaintext attack, differential attack and statistical attack, etc. [ABSTRACT FROM AUTHOR]

In this paper, to enhance the security of double random phase encoding (DRPE), Lorenz system and bidimensional empirical mode decomposition (BEMD) are introduced into an image encryption process. By means of BEMD, the original grayscale image is decomposed into three sub-images, then they are diffused and confused by using the pseudorandom sequences generated by Lorenz system. At last, the three result images are encoded by using DRPE, we obtain the color ciphered image. Thorough experimental tests are carried out with detailed analysis, demonstrating the feasibility and high security of the new scheme. [ABSTRACT FROM AUTHOR]

GPRC6A is proposed to regulate energy metabolism in mice, but in humans a KGKY polymorphism in the third intracellular loop (ICL3) is proposed to result in intracellular retention and loss-of-function. To test physiological importance of this human polymorphism in vivo, we performed targeted genomic humanization of mice by using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9) system to replace the RKLP sequence in the ICL3 of the GPRC6A mouse gene with the uniquely human KGKY sequence to create Gprc6a-KGKY-knockin mice. Knock-in of a human KGKY sequence resulted in a reduction in basal blood glucose levels and increased circulating serum insulin and FGF-21 concentrations. Gprc6a-KGKY-knockin mice demonstrated improved glucose tolerance, despite impaired insulin sensitivity and enhanced pyruvate-mediated gluconeogenesis. Liver transcriptome analysis of Gprc6a-KGKY-knockin mice identified alterations in glucose, glycogen and fat metabolism pathways. Thus, the uniquely human GPRC6A-KGKY variant appears to be a gain-of-function polymorphism that positively regulates energy metabolism in mice. [ABSTRACT FROM AUTHOR]

The authors know that a common and effective way to protect digital images security are to encrypt these images into white noise image. In this study, the authors have designed a new two‐dimensional (2D) chaotic system which is derived from two existing one‐dimensional (1D) chaotic maps. The simulation results show that the new 2D chaotic system is able to produce many 2D chaotic maps by selecting different 1D chaotic maps, and which have the wider chaotic ranges and more complex chaotic behaviours compared with the existing 1D chaotic maps. In order to investigate its applications, using the proposed 2D chaotic maps, the authors design a novel image encryption algorithm. First of all, the original image is scrambled by using the chaotic sequences which are generated by new 2D chaotic maps, Arnold transform and Hilbert curve. Then the scrambled image is confused and diffused by chaotic sequences. Finally, the performance of the proposed encryption algorithm is simulated and the experimental results show that the validity and reliability of the proposed algorithm is validated. [ABSTRACT FROM AUTHOR]

GPRC6A is a widely expressed G-protein coupled receptor that regulates energy metabolism. Global deletion of Gprc6a in mice is reported to result in a metabolic syndrome-like phenotype and conditional deletion of Gprc6a in pancreatic β-cell and skeletal muscle respectively impair insulin secretion and glucose uptake. In the current study, we explore the hepatic functions of GPRC6A by conditionally deleting Gprc6a in hepatocytes by cross breeding Alb-Cre and Gprc6aflox/flox mice to obtain Gprc6aLiver-cko mice. Gprc6aLiver-cko mice on a normal diet showed excessive hepatic fat accumulation and glycogen depletion. These mice also exhibit impaired glucose and pyruvate tolerance, but normal insulin sensitivity. Decreased circulating FGF-21 levels and FGF-21 message expression in the liver were found in Gprc6aLiver-cko mice. Hepatic transcriptome analysis identified alterations in multiple pathways regulating glucose, fat and glycogen metabolism in Gprc6aLiver-cko mice. Taken together, our studies suggest that GPRC6A directly regulates hepatic metabolism as well as regulates the production and release of FGF-21 to control systemic energy homeostasis. GPRC6A's unique regulation of β-cell, skeletal muscle and hepatic function may represent a new therapeutic target for treating disordered energy metabolism metabolic syndrome and type 2 diabetes. [ABSTRACT FROM AUTHOR]

We propose a new image encryption algorithm based on a modified Gerchberg–Saxton algorithm and hyper-chaotic system. First, original image is encoded into a phase function by using the modified Gerchberg–Saxton algorithm, which is controlled by hyper-chaotic system. Then, Josephus traversing is employed to scramble the created phase function. Lastly, the scrambled result is confused and diffused by using hyper-chaotic system simultaneously. The numerical simulations verify the validity and reliability of the proposed scheme. [ABSTRACT FROM AUTHOR]

We propose a new image encryption algorithm based on a modified Gerchberg–Saxton algorithm and hyper-chaotic system. First, original image is encoded into a phase function by using the modified Gerchberg–Saxton algorithm, which is controlled by hyper-chaotic system. Then, Josephus traversing is employed to scramble the created phase function. Lastly, the scrambled result is confused and diffused by using hyper-chaotic system simultaneously. The numerical simulations verify the validity and reliability of the proposed scheme. [ABSTRACT FROM AUTHOR]

New insights into G protein coupled receptor regulation of glucose metabolism by β-cells, skeletal muscle and liver hepatocytes identify GPRC6A as a potential therapeutic target for treating type 2 diabetes mellitus (T2D). Activating GPRC6A with a small molecule drug represents a potential paradigm-shifting opportunity to make significant strides in regulating glucose homeostasis by simultaneously correcting multiple metabolic derangements that underlie T2D, including abnormalities in β-cell proliferation and insulin secretion and peripheral insulin resistance. Using a computational, structure-based high-throughput screening approach, we identified novel tri-phenyl compounds predicted to bind to the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A. Experimental testing found that these compounds dose-dependently stimulated GPRC6A signaling in a heterologous cell expression system. Additional chemical modifications and functional analysis identified one tri-phenyl lead compound, DJ-V-159 that demonstrated the greatest potency in stimulating insulin secretion in β-cells and lowering serum glucose in wild-type mice. Collectively, these studies show that GPRC6A is a “druggable” target for developing chemical probes to treat T2DM. [ABSTRACT FROM AUTHOR]

In this paper, a generalized multi-sawtooth map based image encryption scheme with an efficient permutation-diffusion mechanism is proposed. In the permutation process, a generalized multi-sawtooth map is utilized to generate one chaotic orbit used to get one index order sequence for the permutation of image pixel positions, while in the diffusion process, two generalized multi-sawtooth maps are employed to yield two pseudo-random grey value sequences for a two-way diffusion of pixel grey values. The yielded grey value sequences are not only sensitive to the control parameters and initial conditions of the considered chaotic maps, but also strongly depend on the plain-image processed, therefore the proposed scheme can effectively resist statistical attack, differential attack, known-plaintext as well as chosen-plaintext attack. Experimental results show that the new image encryption scheme has satisfactory security thanks to its large key space and robust permutation-diffusion mechanism, which makes it a potential candidate for designing image encryption schemes. [ABSTRACT FROM AUTHOR]

This paper deals with the classification of the simple higher-order symmetry-breaking bifurcation in multiparameter nonlinear problems with Z2-symmetry. The regular extended systems for computing the simple higher-order symmetry-breaking bifurcation points with different singularities are proposed. An efficient algorithm for solving the extended systems is given. Finally, some numerical examples are shown to demonstrate the efficiency of the algorithm. [ABSTRACT FROM AUTHOR]