Residue-specific structures and membrane locations of pH-low insertion peptide by solid-state nuclear magnetic resonance

The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured but folds across the bilayer as a transmembrane helix at pH similar to 6. Despite their promising applications as imaging probes and drug carriers that target cancer cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP-membrane interactions has not been completely understood. Here, we show the first study on membrane-associated pHLIP using solid-state NMR spectroscopy. Data on residue-specific conformation and membrane location describe pHLIP in various surface-bound and membrane-inserted states at pH 7.4, 6.4 and 5.3. The critical membrane-adsorbed state is more complex than previously envisioned. At pH 6.4, for the major unstructured population, the peptide sinks deeper into the membrane in a state II\u27 that is distinct from the adsorbed state II observed at pH 7.4, which may enable pHLIP to sense slight change in acidity even before insertion

Furanodiene alters mitochondrial function in doxorubicin-resistant MCF-7 human breast cancer cells in an AMPK-dependent manner

Furanodiene is a bioactive sesquiterpene isolated from the spice-producing Curcuma wenyujin plant (Y. H. Chen and C. Ling) (C. wenyujin), which is a commonly prescribed herb used in clinical cancer therapy by modern practitioners of traditional Chinese medicine. Previously, we have shown that furanodiene inhibits breast cancer cell growth both in vitro and in vivo, however, the mechanism for this effect is not yet known. In this study, therefore, we asked (1) whether cultured breast cancer cells made resistant to the chemotherapeutic agent doxorubicin (DOX) via serial selection protocols are susceptible to furanodiene\u27s anticancer effect, and (2) whether AMP-activated protein kinase (AMPK), which is a regulator of cellular energy homeostasis in eukaryotic cells, participates in this effect. We show here (1) that doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells treated with furanodiene exhibit altered mitochondrial function and reduced levels of ATP, resulting in apoptotic cell death, and (2) that AMPK is central to this effect. In these cells, furanodiene (as opposed to doxorubicin) noticeably affects the phosphorylation of AMPK and AMPK pathway intermediates, ACLY and GSK-3β, suggesting that furanodiene reduces mitochondrial function and cellular ATP levels by way of AMPK activation. Finally, we find that the cell permeable agent and AMPK inhibitor compound C (CC), abolishes furanodiene-induced anticancer activity in these MCF-7/DOXR cells, with regard to cell growth inhibition and AMPK activation; in contrast, AICAR (5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside, acadesine), an AMPK activator, augments furanodiene-induced anticancer activity. Furthermore, specific knockdown of AMPK in MCF-7/DOXR cells protects these cells from furanodiene-induced cell death. Taken together, these findings suggest that AMPK and its pathway intermediates are promising therapeutic targets for treating chemoresistant breast cancer, and that furanodiene may be an important chemical agent incorporated in next-generation chemotherapy protocols

Damage modelling: the current state and the latest progress on the development of creep damage constitutive equations for high Cr steels

This paper reviews the fundamentals of the development of creep damage constitutive equations for high Cr steels including (1) a concise summary of the characteristics of creep deformation and creep damage evolution and their dependence on the stress level and the importance of cavitation for the final fracture; (2) a critical review of the state of art of creep damage equation for high Cr steels; (3) some discussion and comments on the various approaches; (4) consideration and suggestion for future work. It emphasises the need for better understanding the nucleation, cavity growth and coalesces and the theory for coupling method between creep cavity damage and brittle fracture and generalisatio

Isospin Effect on the Process of Multifragmentation and Dissipation at Intermediate Energy Heavy Ion Collisions

In the simulation of intermediate energy heavy ion collisions by using the isospin dependent quantum molecular dynamics, the isospin effect on the process of multifragmentation and dissipation has been studied. It is found that the multiplicity of intermediate mass fragments $N_{imf}$ for the neutron-poor colliding system is always larger than that for the neutron-rich system, while the quadrupole of single particle momentum distribution $Q_{zz}$ for the neutron-poor colliding system is smaller than that of the neutron-rich system for all projectile-target combinations studied at the beam energies from about 50MeV/nucleon to 150MeV/nucleon. Since $Q_{zz}$ depends strongly on isospin dependence of in-medium nucleon-nucleon cross section and weakly on symmetry potential at the above beam energies, it may serve as a good probe to extract the information on the in-medium nucleon-nucleon cross section. The correlation between the multiplicity $N_{imf}$ of intermediate mass fragments and the total numer of charged particles $N_c$ has the behavior similar to $Q_{zz}$, which can be used as a complementary probe to the in-medium nucleon-nucleon cross section.Comment: 18 pages, 9 figure

Monsoonal control on a delayed response of sedimentation to the 2008 Wenchuan earthquake

Infrequent extreme events such as large earthquakes pose hazards and have lasting impacts on landscapes and biogeochemical cycles. Sediments provide valuable records of past events, but unambiguously identifying event deposits is challenging because of nonlinear sediment transport processes and poor age control. Here, we have been able to directly track the propagation of a tectonic signal into stratigraphy using reservoir sediments from before and after the 2008 Wenchuan earthquake. Cycles in magnetic susceptibility allow us to define a precise annual chronology and identify the timing and nature of the earthquake’s sedimentary record. The grain size and Rb/Sr ratio of the sediments responded immediately to the earthquake. However, the changes were muted until 2 years after the event, when intense monsoonal runoff drove accumulation of coarser grains and lower Rb/Sr sediments. The delayed response provides insight into how climatic and tectonic agents interact to control sediment transfer and depositional processes.This work was funded by the 2nd Tibetan Plateau Scientific Expedition and Research (2019QZKK0707) and CAS programs (QYZDJ-SSW-DQC033, XDA2007010202, and 132B61KYSB20170008) grants to Z.J. and SKLLQG grant (SKLLQGPY1603) to F.Z

Chaotic Signatures of Heart Rate Variability and Its Power Spectrum in Health, Aging and Heart Failure

A paradox regarding the classic power spectral analysis of heart rate variability (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral peaks represent stochastic or chaotic phenomena. Resolution of this ftitration undamental issue is key to unraveling the mechanisms of HRV, which is critical to its proper use as a noninvasive marker for cardiac mortality risk assessment and stratification in congestive heart failure (CHF) and other cardiac dysfunctions. However, conventional techniques of nonlinear time series analysis generally lack sufficient sensitivity, specificity and robustness to discriminate chaos from random noise, much less quantify the chaos level. Here, we apply a ‘litmus test’ for heartbeat chaos based on a novel noise assay which affords a robust, specific, time-resolved and quantitative measure of the relative chaos level. Noise titration of running short-segment Holter tachograms from healthy subjects revealed circadian-dependent (or sleep/wake-dependent) heartbeat chaos that was linked to the HF component (respiratory sinus arrhythmia). The relative ‘HF chaos’ levels were similar in young and elderly subjects despite proportional age-related decreases in HF and LF power. In contrast, the near-regular heartbeat in CHF patients was primarily nonchaotic except punctuated by undetected ectopic beats and other abnormal beats, causing transient chaos. Such profound circadian-, age- and CHF-dependent changes in the chaotic and spectral characteristics of HRV were accompanied by little changes in approximate entropy, a measure of signal irregularity. The salient chaotic signatures of HRV in these subject groups reveal distinct autonomic, cardiac, respiratory and circadian/sleep-wake mechanisms that distinguish health and aging from CHF

Genetic Characterization of the Soybean Nested Association Mapping Population

A set of nested association mapping (NAM) families was developed by crossing 40 diverse soybean [Glycine max (L.) Merr.] genotypes to the common cultivar. The 41 parents were deeply sequenced for SNP discovery. Based on the polymorphism of the single-nucleotide polymorphisms (SNPs) and other selection criteria, a set of SNPs was selected to be included in the SoyNAM6K BeadChip for genotyping the parents and 5600 RILs from the 40 families. Analysis of the SNP profiles of the RILs showed a low average recombination rate. We constructed genetic linkage maps for each family and a composite linkage map based on recombinant inbred lines (RILs) across the families and identified and annotated 525,772 high confidence SNPs that were used to impute the SNP alleles in the RILs. The segregation distortion in most families significantly favored the alleles from the female parent, and there was no significant difference of residual heterozygosity in the euchromatic vs. heterochromatic regions. The genotypic datasets for the RILs and parents are publicly available and are anticipated to be useful to map quantitative trait loci (QTL) controlling important traits in soybean

Pairing symmetry and properties of iron-based high temperature superconductors

Pairing symmetry is important to indentify the pairing mechanism. The analysis becomes particularly timely and important for the newly discovered iron-based multi-orbital superconductors. From group theory point of view we classified all pairing matrices (in the orbital space) that carry irreducible representations of the system. The quasiparticle gap falls into three categories: full, nodal and gapless. The nodal-gap states show conventional Volovik effect even for on-site pairing. The gapless states are odd in orbital space, have a negative superfluid density and are therefore unstable. In connection to experiments we proposed possible pairing states and implications for the pairing mechanism.Comment: 4 pages, 1 table, 2 figures, polished versio

Comparison of two novel MRAS strategies for identifying parameters in permanent magnet synchronous motors

Two Model Reference Adaptive System (MRAS) estimators are developed for identifying the parameters of permanent magnet synchronous motors (PMSM) based on Lyapunov stability theorem and Popov stability criterion, respectively. The proposed estimators only need online detection of currents, voltages and rotor rotation speed, and are effective in the estimation of stator resistance, inductance and rotor flux-linkage simultaneously. Their performances are compared and verified through simulations and experiments. It shows that the two estimators are simple and have good robustness against parameter variation and are accurate in parameter tracking. However, the estimator based on Popov stability criterion, which can overcome the parameter variation in a practical system, is superior in terms of response speed and convergence speed since there are both proportional and integral units in the estimator in contrast to only one integral unit in the estimator based on Lyapunov stability theorem. In addition, there is no need of the expert experience which is required in designing a Lyapunov function