Search

Hedgehog (Hh) is a morphogen that binds to its receptor Patched 1 and activates Smoothened (SMO), thereby governing embryonic development and postnatal tissue homeostasis. Cholesterol can bind and covalently conjugate to the luminal cysteine-rich domain (CRD) of human SMO at the D95 residue (D99 in mouse). The reaction mechanism and biological function of SMO cholesterylation have not been elucidated. Here, we show that the SMO-CRD undergoes auto-cholesterylation which is boosted by calcium and involves an intramolecular ester intermediate. In cells, Hh stimulation elevates local calcium concentration in the SMO-localized endosomes through store-operated calcium entry. In addition, we identify the signaling-incompetent SMO D95E mutation, and the D95E mutant SMO can bind cholesterol but cannot be modified or activated by cholesterol. The homozygous SmoD99E/D99Eknockin mice are embryonic lethal with severe developmental delay, demonstrating that cholesterylation of CRD is required for full-length SMO activation. Our work reveals the unique autocatalytic mechanism of SMO cholesterylation and an unprecedented role of calcium in Hh signaling.

By combining the traditional iteration structure of Hash function with the dynamic S-boxes, a novel keyed Hash function is presented. The proposed approach can give a chaotic Hash value by means of the lookup table of functions and chaotic dynamic S-box. Compared with the existing chaotic Hash functions, this method improves computational performance of Hash system by using the chaotic S-box substitution. Theoretical and experimental results show that the proposed method has not only strong one way property, sensitivity to initial conditions and chaotic system’s parameters, but also high speed.

A novel keyed Hash function is presented based on the dynamic S-boxes. The proposed approach can give a chaotic Hash value by means of the lookup table of functions and chaotic dynamic S-box. Compared with the existing chaotic Hash functions, this method improves computational performance of Hash system by using the chaotic S-box substitution. Theoretical and experimental results show that the proposed method has not only strong one way property, sensitivity to initial conditions and chaotic system’s parameters, but also high speed.

A secure communication scheme based on piecewise linear chaotic system is proposed. Two Chaotic Systems are used in this algorithm, with a symbolic sequence generated by a Chaotic System the message sequence is tracked, employing the chaotic masking technique the message for transmitted is encrypted with a binary sequence extracted from another Chaotic System. The theoretic and experience results stated that the proposed algorithm has many properties such as high speed and easy implementing and high security and it is suitable for practical use in the secure communication.

Based on particle swarm optimization algorithm, this paper presents a grid scheduling optimization algorithm combing the advantages of Ant Colony optimization algorithm. The algorithm processes task scheduling through particle swarm optimization algorithm to get a group of relatively optimal solutions, and then conducts small-area local search with Ant Colony optimization algorithm. Theoretical analysis and results of the simulation experiments show that this scheduling algorithm effectively achieves load balancing of resources with comprehensive advantages in time efficiency and solution accuracy compared to the traditional Ant Colony optimization algorithm and particle swarm optimizationalgorithm, and can be applied to task scheduling in grid computing.

ABSTRACTGenetic mutations lead to the production of mutated proteins from which peptides are presented to T cells as cancer neoantigens. Evidence suggests that T cells that target neoantigens are the main mediators of effective cancer immunotherapies. Although algorithms have been used to predict neoantigens, only a minority are immunogenic. The factors that influence neoantigen immunogenicity are not completely understood. Here, we classified human neoantigen/neopeptide data into three categories based on their TCR-pMHC binding events. We observed a conservative mutant orientation of the anchor residue from immunogenic neoantigens which we termed the “NP” rule. By integrating this rule with an existing prediction algorithm, we found improved performance in neoantigen prioritization. To better understand this rule, we solved several neoantigen/MHC structures. These structures showed that neoantigens that follow this rule not only increase peptide-MHC binding affinity but also create new TCR-binding features. These molecular insights highlight the value of immune-based classification in neoantigen studies and may enable the design of more effective cancer immunotherapies.

Stomatal movement is strictly regulated by various intracellular and extracellular factors in response environmental signals. In our recent study, we found that an Arabidopsis guard cell expressed expansin, AtEXPA1, regulates stomatal opening by altering the structure of the guard cell wall. This addendum proposes a mechanism by which guard cell expansins regulate stomatal movement.