Helix Formation Research Articles

A comprehensive study of Z-DNA density and its evolutionary implications in birds

BackgroundZ-DNA, a left-handed helical form of DNA, plays a significant role in genomic stability and gene regulation. Its formation, associated with high GC content and repetitive sequences, is linked to genomic instability, potentially leading to large-scale deletions and contributing to phenotypic diversity and evolutionary adaptation.ResultsIn this study, we analyzed the density of Z-DNA-prone motifs of 154 avian genomes using the non-B DNA Motif Search Tool (nBMST). Our findings indicate a higher prevalence of Z-DNA motifs in promoter regions across all avian species compared to other genomic regions. A negative correlation was observed between Z-DNA density and developmental time in birds, suggesting that species with shorter developmental periods tend to have higher Z-DNA densities. This relationship implies that Z-DNA may influence the timing and regulation of development in avian species. Furthermore, Z-DNA density showed associations with traits such as body mass, egg mass, and genome size, highlighting the complex interactions between genome architecture and phenotypic characteristics. Gene Ontology (GO) analysis revealed that Z-DNA motifs are enriched in genes involved in nucleic acid binding, kinase activity, and translation regulation, suggesting a role in fine-tuning gene expression essential for cellular functions and responses to environmental changes. Additionally, the potential of Z-DNA to drive genomic instability and facilitate adaptive evolution underscores its importance in shaping phenotypic diversity.ConclusionsThis study emphasizes the role of Z-DNA as a dynamic genomic element contributing to gene regulation, genomic stability, and phenotypic diversity in avian species. Future research should experimentally validate these associations and explore the molecular mechanisms by which Z-DNA influences avian biology.

Unraveling the role of counter ions in shaping the structures of helical peptides in aqueous phase

AbstractHelical peptides, as well as proteins composed of helical peptides, play essential roles in various biological processes, including their functions as components of cell membranes and their interactions with biological membranes. Therefore, it is crucial to predict the propensity and structural characteristics of helices formed in solution or lipid environments for specific peptide sequences. Melittin and pexiganan are antimicrobial peptides (AMPs) that possess distinct sequence characteristics but exhibit similar structural properties in both solution and lipid environments. In this study, we conducted molecular dynamics simulations to investigate how the presence of counter ions creates differences in structural characteristics between these two peptides in solution. By analyzing the structures formed for each AMP using extended helical projections, we aimed to uncover the underlying principles governing the interaction between counter ions and peptide sequences, leading to the formation of stable structures. It was found that the coordination of counter ions effectively extends the helical surface and stabilizes the extended helix by reducing the electrostatic repulsion between charged residues. Our results demonstrate how sequence specificity influences helical structure formation in solution and provide an explanation for the varying degrees of synergistic effects exhibited by different helical AMPs.

Optimizing prolyl hydroxylation for functional recombinant collagen in Escherichia coli

Collagen, a key extracellular matrix component, is renowned for its biocompatibility, biodegradability, and bioactivity, finding wide applications in food, medicine, cosmetics, and industry. Recombinant collagen expression in Escherichia coli offers advantages such as shorter production cycles and lower costs compared to extraction from animal tissues, though it is known to lack essential post-translational modifications, such as proline hydroxylation, which are crucial for its stability and biological function. Studies have shown that certain prolyl hydroxylases, including BaP4H, DsP4H, and L593, exhibit relatively high modification efficiency in the E. coli expression system. However, structures and functions of recombinant human type III collagen after modification by three prolyl hydroxylases remain uncertain. In this study, we investigated the percentage of proline hydroxylation, hydroxylation sites, circular dichroism spectra, and biological functions of recombinant human type III collagen modified by various prolyl hydroxylases. The results indicated that the L593 exhibited the highest percentage of proline hydroxylation, and the percentage of proline hydroxylation was closely associated with the formation of the collagen triple helix, while the hydroxylation ratio of prolines is not positively correlated with the stability of the collagen triple helix structure. The biological function results showed that the cell adhesion of recombinant collagen 3-3(BaP4H) and 3-3(L593) was significantly enhanced, which was closely related to the triple helix structure of recombinant human type III collagen. Our study provides valuable insights into the industrial production and biological applications of collagen, enhancing its functional research and scalability.

Chip formation analysis during dry turning of C45 steel

Machining is a material removal process that creates surfaces through chip formation using a cutting tool. The morphology of the chips and the mechanisms governing their formation directly affect the quality of machined parts. This experimental study examines chip formation mechanisms in the dry turning of C45 steel under various cutting conditions, utilizing coated carbide inserts. Machining performance was evaluated based on key chip morphology parameters, including shape, length, thickness, and volume. The results show that increasing cutting speed (Vc) produces shorter, thicker chips without significantly altering their predominantly helical shape. A higher feed rate (f) maintains the tangled ribbon form of the chips but leads to longer chip production. Additionally, changes in the depth of cut (ap) create instabilities that result in varied chip morphologies, including long tubular, short helical, and elementary forms. As the depth of cut increases, chips become shorter and thinner. These findings provide valuable insights into the material's deformation and fracture mechanisms, enhancing our understanding of chip formation and its impact on the efficiency of dry turning operations on C45 steel.

Commercial Space Industry Development from the Perspective of the Triple Helix: Evidence from China and the United States

Abstract: The university-industry-government triple helix has been an ideal approach to interpret the growth of innovative industries, especially in the context of todays technological leap. This study examines the commercial space sectors in United States and China, the two leading space powers, to analyze how the triple helix structures evolve and synergize to shape their respective industries. It is found that in the United States, the helix is rooted in legislation and procurement support, spurred by a well-developed industrial system, and reinforced by extensive enterprise-university collaboration programs. In contrast, the Chinese triple helix formation trajectory begins with experimental policies and space infrastructure construction, evolves through enterprises considered positioning in reusable rocket and satellite internet, and is potentially propelled by an expanding scale of talents exiting state-owned space institutions or fostered by emerging academies. After that, a lateral comparison between the two triple-helix models is undertaken to unveil the characteristics, similarities, and disparities within the commercial space industries of these two nations. This paper concludes that, for nations aiming at establishing a commercially sustainable space industry, the essence lies in a fully developed triple helix where efforts of government, industry, and academia can systematically converge without significant lag in any aspect. The paper also mentions the potential benefits of commercial space cooperation between the United States and China.

Remarkable Stability of Glutathione-Based Supramolecular Gel in the Presence of Oxidative Stress from Hydrogen Peroxide.

Low molecular weight 7-methoxy-3-(p-nitrophenyl)iminocoumarin (MNI) with donor and acceptor groups has been synthesized. The molecule shows typical π-stacking geometry in the crystal structure. In this study, MNI, an achiral small organic molecule, forms a nanostructured supramolecular gel along with a short peptide sequence glutathione (GSH). The self-assembly of the achiral organic coumarin component and chiral biomolecule produces a chiral gel with helical fiber structures. Interestingly, the helicities of chiral gels are controlled by the solvent ratio, where MNI in DMSO and GSH in water has been used. Variation of the solvent ratio from 6:4 to 1:9 for DMSO:H2O results in six gels (4, 5, 6, 7, 8 and 9), where the gel numbers signify the water content ratio. FE-SEM analysis shows gel fibers with right-handed helical structures, which have been further confirmed by circular dichroism (CD) with notable helicity in 4 to 6. This is the first report of controlled chiral helical nanostructured supramolecular gel formation by a solvent mixture with an organic small molecule and biomolecule. Interestingly, storage modulus (G') initially decreases from 4 to 6 and further increases up to 9. An opposite strain (%) trend was observed among these six gels. These unusual solvent-dependent gel properties have been further applied to monitor the stability of the gels in the presence of hydrogen peroxide (H2O2), which converts GSH to oxidized glutathione (GSSG) in general. The oxidative stress from H2O2 disrupts 4 to 6 gels, and precipitation occurs. It is noteworthy to mention that GSSG alone cannot form a gel with the MNI molecule and forms a precipitate. Remarkably, on the other hand, 7 to 9 remain as strong gels even after H2O2 treatment. Among all six gels, 9 shows extraordinary stability of gels even after H2O2 treatment.

Statistical analysis of the unique characteristics of secondary structures in proteins

Protein folding is a complex process influenced by the primary sequence of amino acids. Early studies focused on understanding whether the specificity or the conservation of properties of amino acids was crucial for folding into secondary structures such as α-helices, β-sheets, turns, and coils. However, with the advent of artificial intelligence (AI) and machine learning (ML), the emphasis has shifted towards the precise nature and occurrence of specific amino acids. In our study, we analyzed a large set of proteins from diverse organisms to identify unique features of secondary structures, particularly in terms of the distribution of polar, non-polar, and charged amino acid residues. We found that α-helices tend to have a higher proportion of charged and non-polar groups compared to other secondary structures and that the presence of oppositely charged amino acid residues in helices stabilizes them, facilitating the formation of longer helices. These characteristics are distinct to α-helices. This study offers valuable insights for researchers in the field of protein design, enabling the de-novo creation of short helical peptides for a range of applications. We have also developed a web server for extensive analysis of proteins from different databases. The web server is housed at https://proseqanalyser.iitgn.ac.in/

Riboswitch Mechanisms for Regulation of P1 Helix Stability.

Riboswitches are highly structured RNA regulators of gene expression. Although found in all three domains of life, they are particularly abundant and widespread in bacteria, including many human pathogens, thus making them an attractive target for antimicrobial development. Moreover, the functional versatility of riboswitches to recognize a myriad of ligands, including ions, amino acids, and diverse small-molecule metabolites, has enabled the generation of synthetic aptamers that have been used as molecular probes, sensors, and regulatory RNA devices. Generally speaking, a riboswitch consists of a ligand-sensing aptamer domain and an expression platform, whose genetic control is achieved through the formation of mutually exclusive secondary structures in a ligand-dependent manner. For most riboswitches, this involves formation of the aptamer's P1 helix and the regulation of its stability, whose competing structure turns gene expression ON/OFF at the level of transcription or translation. Structural knowledge of the conformational changes involving the P1 regulatory helix, therefore, is essential in understanding the structural basis for ligand-induced conformational switching. This review provides a summary of riboswitch cases for which ligand-free and ligand-bound structures have been determined. Comparative analyses of these structures illustrate the uniqueness of these riboswitches, not only in ligand sensing but also in the various structural mechanisms used to achieve the same end of regulating switch helix stability. In all cases, the ligand stabilizes the P1 helix primarily through coaxial stacking interactions that promote helical continuity.

4D-Flow MRI and Vector Ultrasound in the In-Vitro Evaluation of Surgical Aortic Heart Valves - a Pilot Study.

The aim of this study was the initial investigation of 4D-Flow MRI and Vector Ultrasound as novel imaging techniques in the in-vitro analysis of hemodynamics in anatomical models. Specifically, by looking at the hemodynamic performance of state-of-the-art surgical heart valves in a 3D-printed aortic arch. The mock circulatory loop simulated physiological, pulsatile flow. Two mechanical and three biological aortic valves prostheses were compared in a 3D-printed aortic arch. 4D magnetic resonance imaging and vector flow Doppler ultrasound served as imaging methods. Hemodynamic parameters such as wall shear stress, flow velocities and pressure gradients were analyzed. The flow analysis revealed characteristic flow-patterns in the 3D-printed aortic arch. The blood-flow in the arch presented complex patterns, including the formation of helixes and vortices. Higher proximal peak velocities and lower flow volumes were found for biological valves. The mock circulatory loop in combination with modern radiological imaging provides a sufficient basis for the hemodynamic comparison of aortic valves.

Fluorine-Thiol Displacement Stapling on the Disordered αB of pKID Domain Increases Its Helicity and Affinity to KIX

AbstractThe development of high-affinity ligands specifically targeting intrinsically disordered protein interactions has remained challenging due to the lack of well-defined binding pockets and shallow binding surfaces commonly found at their interfaces. Here, we employed our fluorine-thiol displacement reaction (FTDR) peptide-stapling platform to synthesize a library of peptide-based ligands derived from the αB-helix of the disordered pKID to target its binding partner KIX. Our library revealed that helical formation and affinity to KIX is highly favored when the αB peptide was stapled at sites corresponding to Arg135 and Ser142, further supporting the hypothesis that stabilization of αB significantly influences the overall binding affinity of pKID to KIX. We also found that the highest binding peptide, αB-RSpS, may form secondary contacts at the MLL site on KIX in addition to binding at the primary pKID site. Lastly, no binding to KIX was observed for any αB-stapled peptide that lacked the conserved helix-flanking prolines Pro132 and Pro146. Conserved helix-flanking prolines have previously been shown to modulate the binding affinities of other disordered domains in other proteins including MLL and p53. However, to our knowledge this is the first evidence within αB of pKID.

Geometric Parameter Optimization for Axial Modification in Helical Gear Form Grinding

During the axial modification in helical gear form grinding, the contact line between the grinding wheel and the gear constantly changes, and the additional radial motion can cause a “tooth surface twist” phenomenon. An optimization method for tooth surface twist error was proposed to address this. Based on the gear meshing principles, a mathematical model for axial modification in form grinding was established to solve for the instantaneous contact lines at various positions on the actual modified tooth surface. By analyzing the influence of the grinding wheel installation angle on the axial modification contact line, an optimization model was constructed to reduce the twist of the transverse profile, reduce the twist of the flank profile, reduce the helix deviation, and improve the form grinding efficiency. The practical implications of this research are significant, as the Particle Swarm Optimization (PSO) algorithm was employed to optimize the form grinding parameters, leading to a method that effectively reduced tooth surface twist error and improved the form grinding accuracy of the modified tooth surface.

Self-assembly of mixed-linkage glucan hydrogels formed following EG16 digestion

Mixed-linkage glucans are major components of grassy cell-walls and cereal endosperm. Recently identified plant endo-β-glucanase from the EG16 family cleaves MLGs with strong specificity towards regions with at least four sequential β(1,4)-linked glucose residues. This activity yields a low molecular-weight MLG with a repeating structure of β(1,3)-linked cellotriose that gels rapidly at concentrations as low as 1.0 % w/v. To understand the gelation mechanism, we investigated the structure and behavior using rheology, microscopy, X-ray scattering, and molecular dynamics simulations. Upon digestion, the material's rheological behavior changes from typical polymeric material to a fibrillar network behavior seen for e.g. cellulose nanofibrils. Scanning electron microscopy and confocal microscopy verifies these changes in micro- and nanostructure. Small-angle X-ray scattering shows in-solution self-assembly of MLG through ~10 nm elemental structures. Wide-angle X-ray scattering data indicate that the polymer association is similar to cellulose II, with dominant scattering at d-spacing of 0.43 nm. Simulations of two interacting glucan chains show that β(1,3)-linkages prevent the formation of tight helices that form between β(1,4)-linked d-glucan chains, leading to weaker interactions and less ordered inter-chain assembly. Overall, these data indicate that digestion drives gelation not by enhancement of interactions driving self-assembly, but by elimination of unproductive interactions hindering self-assembly.

A Newly Identified Peripheral Duplex Anchors and Stabilizes the MALAT1 Triplex.

The accumulation of the 8-kb oncogenic long noncoding MALAT1 RNA in cells is dependent on the presence of a protective triple helix structure at the 3' terminus. While recent studies have examined the functional importance of numerous base triples within the triplex and its immediately adjacent base pairs, the functional importance of peripheral duplex elements has not been thoroughly investigated. To investigate the functional importance of a peripheral linker region that was previously described as unstructured, we employed a variety of assays including thermal melting, protection from exonucleolytic degradation by RNase R, small-angle X-ray scattering, biochemical ligation and binding assays, and computational modeling. Our results demonstrate the presence of a duplex within this linker that enhances the functional stability of the triplex in vitro, despite its location more than 40 Å from the 3' terminus. We present a full-length model of the MALAT1 triple helix-containing RNA having an extended rod-like structure and comprising 33 layers of coaxial stacking interactions. Taken together with recent research on a homologous triplex, our results demonstrate that peripheral elements anchor and stabilize triplexes in vitro. Such peripheral elements may also contribute to the formation and stability of some triple helices in vivo.

Effect of branch length of cluster dextrin on the textural and rheological properties of κ-carrageenan emulsion gels

In this paper, a range of novel cluster dextrins (CDs) with high molecular weight (∼105 g/mol) and narrow molecular weight distribution were fabricated by α-amylase and branching enzyme (BE, EC 2.4.1.18). The influence of CDs on the physicochemical properties of κ-carrageenan (KC) emulsion gels was investigated. The average particle size of the composite emulsion gels containing CD was decreased by 7.85–12.66 μm, and the gel network was more uniform and denser, owing to stronger non-covalent interactions in the composite sample system. Textural results demonstrated that the composite emulsion gels exhibited higher hardness and springiness, but lower cohesiveness. CDs hindered the formation and aggregation of KC double helices, as evidenced by reducing the intensity of the sulfate group peak at 1223 cm−1. Furthermore, CDs increased the apparent viscosity, storage modulus (G'), and melting temperature (Tm) of emulsion gels, based on rheological results. CDs with longer branch lengths were more prone to entangle with KC chains to optimize the gel structure, exhibiting a more significant effect on the physicochemical properties of emulsion gels. The present study provided a new insight for constructing a new energy delivery system.

WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation

One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12–ATG5–ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b’s association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b’s association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis.

Numerical simulation and in vitro experimental study of the hemodynamic performance of vena cava filters with helical forms

Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid–structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

Effect of annulus ratio on the residence time distribution and Péclet number in micro/milli‐scale reactors

AbstractMicro/milli‐scale annular reactor with straight and helical forms has excellent heat and mass transfer performance due to the short molecular diffusion distance and dual‐wall surface transport. The annular gap spacing is scalable by adjusting the inner and outer tube diameter. The influence of diffusion and convection effects on axial dispersion as expanding the flow scale requires further elucidation with the help of residence time distribution (RTD) curves and Péclet (Pe) numbers. The correlation of RTD characteristics with annulus ratio γ = Dh/D (ratio of annulus characteristic size to outer diameter) is investigated using computational fluid dynamics. Results show that with enlarging the straight annular gap from micro‐scale to milli‐scale, RTD characteristics exhibit opposing patterns. This can be attributed to the transition from diffusion‐dominated to convection‐dominated on momentum transfer, and the transition interval is 0.167 < γ < 0.250. Correlation equations of Pe number with Reynolds (Re) number and γ are established under diffusion‐dominated and convection‐dominated states. The symmetrically distributed secondary flow in the helical annular gap effectively elevates the Pe (Pemax > 100). Correlation equations of Pe with Re and γ are established in helical annular gaps with 0.083 < γ < 0.208 and 0.167 < γ < 0.500. The above results contribute to understanding the annular flow RTD characteristics for better applications of tube‐in‐tube reactors.

Assembly of the bacterial ribosome with circularly permuted rRNA.

Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the structural insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate during in vitro ribosome synthesis using a set of circularly permuted (CiPer) rRNAs. The observed ensemble of 23 resolved ribosome large subunit intermediates reveals conserved assembly routes with an underlying hierarchy among cooperative assembly blocks. There are intricate interdependencies for the formation of key structural rRNA helices revealed from the circular permutation of rRNA. While the order of domain synthesis is not obligatory, the order of domain association does appear to proceed with a particular order, likely due to the strong evolutionary pressure on efficient ribosome synthesis. This work reinforces the robustness of the known assembly hierarchy of the bacterial large ribosomal subunit and offers a coherent view of how efficient assembly of CiPer rRNAs can be understood in that context.

Conformational Properties of Poly(A)-Binding Protein Complexed with Poly(A) RNA.

Microscopic understanding of protein-RNA interactions is important for different biological activities, such as RNA transport, translation, splicing, silencing, etc. Polyadenine (Poly(A)) binding proteins (PABPs) make up a class of regulatory proteins that play critical roles in protecting the poly(A) tails of cellular mRNAs from nuclease degradation. In this work, we performed molecular dynamics simulations to investigate the conformational modifications of human PABP protein and poly(A) RNA that occur during complexation. It is demonstrated that the intermediate linker domain of the protein transforms from a disordered coil-like structure to a helical form during the recognition process, leading to the formation of the complex. On the other hand, disordered collapsed coil-like RNA on complexation has been found to transform into a rigid extended conformation. Importantly, the binding free energy calculation showed that the thermodynamic stability of the complex is primarily guided by favorable hydrophobic interactions between the protein and the RNA.

Mild alkali treatment alters structure and properties of maize starch: The potential role of alkali in starch chemical modification

Normal and waxy maize starches were treated with mild alkali treatment (pH 8.5, 9.9, 11.3) in two temperature-time combinations (25 °C for 1 h and 50 °C for 18 h) to investigate the effect on starch structure and properties. Mild alkali treatment partly removed the starch granule-associated proteins and lipids of normal (from 0.31 % to 0.24 % and from 0.77 % to 0.55 %, respectively) and waxy maize starches (from 0.22 % to 0.18 % and from 0.24 % to 0.15 %, respectively). Gelatinization enthalpy of waxy maize starch increased with alkali treatment from 16.20 J·g−1 to 21.95 J·g−1, indicating that amylopectin (AP) rearrangement and AP-AP double helices formation might occur. But amylose could inhibit these effects by restricting mobility of amylopectin, and no such changes occurred for normal maize starch. Alkali treatment decreased gelatinization temperature and increased peak and final viscosity. Alkali treatment decreased trough viscosity and increased setback of normal maize starch. The hydrothermal treatment promoted the effect of alkali, attributed to the more rapid molecular motion at higher temperature. Normal and waxy starches showed different changes after alkali treatment, indicating that amylose played an important role in controlling the effect of alkali and hydrothermal treatment, primarily as an obstructer of amylopectin rearrangement in mild alkali treatment.