PhD

dissertationGuanine-rich DNA/RNA sequences have the potential to form four-stranded structures called G-quadruplexes. Because of the rigidity and glycosidic bond orientation diversity in the stems, the flexibility of loops, and the featured alignment of several cations within one quadruplex channel, G-quadruplexes can serve as a sensitive benchmark to assess and validate current force fields for nucleic acids in molecular dynamics (MD) simulations

An Integrated Ecological Approach to Mapping Variations in Collectivism Within China: Introducing the Triple-Line Framework

Measurable regional variations in collectivism have been found across the Chinese mainland, challenging the simple classification of China as a &quot;collectivistic society&quot; in cross-national studies. In previous studies, a small number of distal or proximal ecological factors have been used to explain these regional variations of collectivism. However, there has been little consensus on which ecological factors best predict regional collectivism. In this article, the authors propose the &quot;triple-line framework,&quot; an integrated perspective on regional variations in collectivism. This framework divides China into four regions using three lines-the Hu Huanyong Line, the Great Wall Line, and the Qinling-Huaihe Line-according to their ecological, historical, and social characteristics. A growing body of empirical research is largely consistent with this framework. The authors conclude by discussing the potential for this framework to generate new, testable hypotheses and consider some ways in which this approach to intranational variation could be used by cultural psychologists working in other parts of the world.</p

Function-Related Asymmetry of the Interactions between Matrix Loops and Conserved Sequence Motifs in the Mitochondrial ADP/ATP Carrier

The ADP/ATP carrier (AAC) plays a central role in oxidative metabolism by exchanging ATP and ADP across the inner mitochondrial membrane. Previous experiments have shown the involvement of the matrix loops of AAC in its function, yet potential mechanisms remain largely elusive. One obstacle is the limited information on the structural dynamics of the matrix loops. In the current work, unbiased all-atom molecular dynamics (MD) simulations were carried out on c-state wild-type AAC and mutants. Our results reveal that: (1) two ends of a matrix loop are tethered through interactions between the residue of triplet 38 (Q38, D143 and Q240) located at the C-end of the odd-numbered helix and residues of the [YF]xG motif located before the N-end of the short matrix helix in the same domain; (2) the initial progression direction of a matrix loop is determined by interactions between the negatively charged residue of the [DE]G motif located at the C-end of the short matrix helix and the capping arginine (R30, R139 and R236) in the previous domain; (3) the two chemically similar residues D and E in the highly conserved [DE]G motif are actually quite different; (4) the N-end of the M3 loop is clamped by the [DE]G motif and the capping arginine of domain 2 from the two sides, which strengthens interactions between domain 2 and domain 3; and (5) a highly asymmetric stable core exists within domains 2 and 3 at the m-gate level. Moreover, our results help explain almost all extremely conserved residues within the matrix loops of the ADP/ATP carriers from a structural point of view. Taken together, the current work highlights asymmetry in the three matrix loops and implies a close relationship between asymmetry and ADP/ATP transport

Investigating the Broad Matrix-Gate Network in the Mitochondrial ADP/ATP Carrier through Molecular Dynamics Simulations

The mitochondrial ADP/ATP carrier (AAC) exports ATP and imports ADP through alternating between cytosol-open (c-) and matrix-open (m-) states. The salt bridge networks near the matrix side (m-gate) and cytosol side (c-gate) are thought to be crucial for state transitions, yet our knowledge on these networks is still limited. In the current work, we focus on more conserved m-gate network in the c-state AAC. All-atom molecular dynamics (MD) simulations on a variety of mutants and the CATR-AAC complex have revealed that: (1) without involvement of other positive residues, the charged residues from the three Px[DE]xx[KR] motifs only are prone to form symmetrical inter-helical network; (2) R235 plays a determinant role for the asymmetry in m-gate network of AAC; (3) R235 significantly strengthens the interactions between H3 and H5; (4) R79 exhibits more significant impact on m-gate than R279; (5) CATR promotes symmetry in m-gate mainly through separating R234 from D231 and fixing R79; (6) vulnerability of the H2-H3 interface near matrix side could be functionally important. Our results provide new insights into the highly conserved yet variable m-gate network in the big mitochondrial carrier family

Insight into G-DNA Structural Polymorphism and Folding from Sequence and Loop Connectivity through Free Energy Analysis

The lengths of G-tracts and their connecting loop sequences determine G-quadruplex folding and stability. Complete understanding of the sequence–structure relationships remains elusive. Here, single-loop G-quadruplexes were investigated using explicit solvent molecular dynamics (MD) simulations to characterize the effect of loop length, loop sequence, and G-tract length on the folding topologies and stability of G-quadruplexes. Eight loop types, including different variants of lateral, diagonal, and propeller loops, and six different loop sequences [d0 (i.e., no intervening residues in the loop), dT, dT₂, dT₃, dTTA, and dT₄] were considered through MD simulation and free energy analysis. In most cases the free energetic estimates agree well with the experimental observations. The work also provides new insight into G-quadruplex folding and stability. This includes reporting the observed instability of the left propeller loop, which extends the rules for G-quadruplex folding. We also suggest a plausible explanation why human telomere sequences predominantly form hybrid-I and hybrid-II type structures in K⁺ solution. Overall, our calculation results indicate that short loops generally are less stable than longer loops, and we hypothesize that the extreme stability of sequences with very short loops could possibly derive from the formation of parallel multimers. The results suggest that free energy differences, estimated from MD and free energy analysis with current force fields and simulation protocols, are able to complement experiment and to help dissect and explain loop sequence, loop length, and G-tract length and orientation influences on G-quadruplex structure

Conceptions of the good, rivalry, and liberal neutrality

Liberal neutrality is assumed to pertain to rival conceptions of the good. The nature of the rivalry between conceptions of the good is pivotal to the coherence, scope and realisation of liberal neutrality. Yet, liberal theorists have said very little about rivalry. This paper attempts to fill this gap by reviewing three conceptions of rivalry: incompatibility rivalry, intra-domain rivalry and state power rivalry. I argue that state power rivalry is the morally relevant conception of rivalry, and that it has significant implications for the scope and realisation of liberal neutrality. I conclude that in the light of state power rivalry, the only feasible liberal neutral state is a very minimal one