While global longitudinal strain (GLS) is considered to be a sensitive marker of left ventricular (LV) function, it is significantly influenced by loading conditions. We hypothesized that global myocardial work index (GMWI), a novel marker of LV function, may show better correlation with load-independent markers of LV contractility in rat models of pressure-induced or volume overload-induced heart failure. Male Wistar rats underwent either transverse aortic constriction (TAC; n=12) or aortocaval fistula creation (ACF; n=12), inducing LV pressure or volume overload, respectively. Sham procedures were performed to establish control groups (n=12/12). Echocardiographic loops were obtained to determine GLS and GMWI. Pressure-volume analysis with transient occlusion of the inferior caval vein was carried out to calculate preload recruitable stroke work (PRSW), a load-independent 'gold-standard' parameter of LV contractility. Myocardial samples were collected to assess interstitial and perivascular fibrosis areafluenced by loading conditions, GLS may not be a reliable marker of LV contractility in heart failure induced by pressure or volume overload. GMWI better reflects contractility in haemodynamic overload states, making it a more robust marker of systolic function, while GLS should be considered as an integrative marker, incorporating systolic function, haemodynamic loading state, and adverse tissue remodelling of the LV.Being significantly influenced by loading conditions, GLS may not be a reliable marker of LV contractility in heart failure induced by pressure or volume overload. GMWI better reflects contractility in haemodynamic overload states, making it a more robust marker of systolic function, while GLS should be considered as an integrative marker, incorporating systolic function, haemodynamic loading state, and adverse tissue remodelling of the LV.An RNA structure prediction from a single-sequence RNA folding program is not evidence for an RNA whose structure is important for function. Random sequences have plausible and complex predicted structures not easily distinguishable from those of structural RNAs. How to tell when an RNA has a conserved structure is a question that requires looking at the evolutionary signature left by the conserved RNA. This question is important not just for long noncoding RNAs which usually lack an identified function, but also for RNA binding protein motifs which can be single stranded RNAs or structures. Here we review recent advances using sequence and structural analysis to determine when RNA structure is conserved or not. Although covariation measures assess structural RNA conservation, one must distinguish covariation due to RNA structure from covariation due to independent phylogenetic substitutions. We review a statistical test to measure false positives expected under the null hypothesis of phylogenetic covariation alone (specificity). We also review a complementary test that measures power, that is, expected covariation derived from sequence variation alone (sensitivity). Power in the absence of covariation signals the absence of a conserved RNA structure. We analyze artifacts that falsely identify conserved RNA structure such as the misuse of programs that do not assess significance, the use of inappropriate statistics confounded by signals other than covariation, or misalignments that induce spurious covariation. Among artifacts that obscure the signal of a conserved RNA structure, we discuss the inclusion of pseudogenes in alignments which increase power but destroy covariation. This article is categorized under RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Evolution and Genomics > Computational Analyses of RNA RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.Dopamine transporter (DAT) and sigma-1 receptor (σ1R) are potential therapeutic targets to reduce the psychostimulant effects induced by methamphetamine (METH). Interaction of σ1R with DAT could modulate the binding of METH, but the molecular basis of the association of the two transmembrane proteins and how their interactions mediate the binding of METH to DAT or σ1R remain unclear. Here, we characterize the protein-ligand and protein-protein interactions at a molecular level by various theoretical approaches. The present results show that METH adopts a different binding pose in the binding pocket of σ1R and is more likely to act as an agonist. The relatively lower binding affinity of METH to σ1R supports the role of antagonists as inhibitors that protect against METH-induced effects. We demonstrate that σ1R could bind to Drosophila melanogaster DAT (dDAT) through interactions with either the transmembrane helix α12 or α5 of dDAT. BAY 11-7082 chemical structure Our results showed that the truncated σ1R displays stronger association with dDAT than the full-length σ1R. Although different helix-helix interactions between σ1R and dDAT lead to distinct effects on the dynamics of individual protein, both associations attenuate the binding affinity of METH to dDAT, particularly in the interactions with the helix α5 of dDAT. Together, the present study provides the first computational investigation on the molecular mechanism of coupling METH binding and the association of σ1R with dDAT.Lithium-sulfur (Li-S) batteries are a promising candidate for the next-generation energy storage system, yet their commercialization is primarily hindered by polysulfide shuttling and uncontrollable Li dendrite growth. Here, a protein-based Janus separator was designed and fabricated for suppressing both the shuttle effect and dendrite growth, while facilitating the Li+ transport. The Li metal-protecting layer was a protein/MoS2 nanofabric with high ionic conductivity and good Li+ affinity, thus capable of homogenizing the Li+ flux and facilitating the Li+ transport. The polysulfide-trapping layer was a conductive protein nanofabric enabling strong chemical/electrostatic interactions with polysulfides. Combination of the two layers was achieved by an integrated electrospinning method, yielding a robust and integral Janus separator. As a result, a long-lived symmetric Li|Li cell (>700 h) with stable cycling performance was demonstrated. More significantly, the resulting Li-S battery delivered greatly improved electrochemical performance, including excellent rate capacity and remarkable cycle stability (with a low decay rate of 0.