Gelling properties of myosin as affected by L-lysine and L-arginine by changing the main molecular forces and microstructure

<p>This paper investigated the effects of l-lysine (Lys) and l-arginine (Arg) on the water-holding capacity (WHC) and hardness of myosin gel as well as the mechanism of these effects. The results showed that Lys, Arg, and KOH increased the WHC but decreased the hardness in all cases. At pH 6.32, the WHC increased in the order control < KOH < Lys ≈ Arg, while the hardness decreased in the order control > KOH > Lys > Arg. Lys shortened low field nuclear magnetic resonance spin-spin relaxation times (T₂), while Arg and KOH slightly affected T₂. Lys, Arg, and KOH had different influences on the molecular forces in myosin gels and the distribution of myosin size. Lys formed a gel with porous clusters, while Arg generated a gel with fine caves. Therefore, both Lys and Arg changed the microstructure of myosin gel by changing the distribution of the myosin size as well as the molecular forces that form and/or maintain myosin gel, ultimately contributing to the differences in the WHC, hardness, and T₂.</p

Data_Sheet_1_Prognostic value of plasma phenylalanine and gut microbiota-derived metabolite phenylacetylglutamine in coronary in-stent restenosis.docx

ObjectiveThis study was designed to explore the predictive value of plasma phenylalanine (Phe) and gut microbiota-derived metabolite phenylacetylglutamine (PAGln) in coronary in-stent restenosis (ISR).MethodsPatients with coronary ISR, in-stent hyperplasia (ISH), and in-stent patency (ISP) were retrospectively enrolled in this study. Multivariable logistic regression analyses were used to identify independent risk factors of ISR. The predictive value of plasma Phe and PAGln levels was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the ROC curve (AUCs) were compared using the Z-test. The correlation between PAGln and clinical characteristics were examined using Spearman's correlation analysis.ResultsSeventy-two patients (mean age, 64.74 ± 9.47 years) were divided into three groups according to coronary stent patency: ISR (n = 28), ISH (n = 11), and ISP (n = 33) groups. The plasma levels of Phe and PAGln were significantly higher in the ISR group than in the ISP group. PAGln was positively associated with the erythrocyte sedimentation rate, homocysteine, SYNTAX score, triglyceride to high-density lipoprotein ratio, Phe, and microbiota-related intermediate metabolite phenylacetic acid (PA). In the ISR group, with the aggravation of restenosis, PAGln levels were also elevated. In multivariate regression analyses, Phe, PAGln and SYNTAX score were independent predictors of coronary ISR (all P ConclusionPlasma Phe and PAGln are valuable indices for predicting coronary ISR, and gut microbes may be a promising intervention target to prevent ISR progression.</p

Temporally Controlled Targeting of 4‑Hydroxynonenal to Specific Proteins in Living Cells

In-depth chemical understanding of complex biological processes hinges upon the ability to systematically perturb individual systems. However, current approaches to study impacts of biologically relevant reactive small molecules involve bathing of the entire cell or isolated organelle with excess amounts, leading to off-target effects. The resultant lack of biochemical specificity has plagued our understanding of how biological electrophiles mediate signal transduction or regulate responses that confer defense mechanisms to cellular electrophilic stress. Here we introduce a target-specific electrophile delivery platform that will ultimately pave the way to interrogate effects of reactive electrophiles on specific target proteins in cells. The new methodology is demonstrated by photoinducible targeted delivery of 4-hydroxynonenal (HNE) to the proteins Keap1 and PTEN. Covalent conjugation of the HNE-precursor to HaloTag fused to the target proteins enables directed HNE delivery upon photoactivation. The strategy provides proof of concept of selective delivery of reactive electrophiles to individual electrophile-responsive proteins in mammalian cells. It opens a new avenue enabling more precise determination of the pathophysiological consequences of HNE-induced chemical modifications on specific target proteins in cells

Developing Bivalent Ligands to Target CUG Triplet Repeats, the Causative Agent of Myotonic Dystrophy Type 1

An expanded CUG repeat transcript (CUG^exp) is the causative agent of myotonic dystrophy type 1 (DM1) by sequestering muscleblind-like 1 protein (MBNL1), a regulator of alternative splicing. On the basis of a ligand (<b>1</b>) that was previously reported to be active in an in vitro assay, we present the synthesis of a small library containing 10 dimeric ligands (<b>4</b>–<b>13</b>) that differ in length, composition, and attachment point of the linking chain. The oligoamino linkers gave a greater gain in affinity for CUG RNA and were more effective when compared to oligoether linkers. The most potent in vitro ligand (<b>9</b>) was shown to be aqueous-soluble and both cell- and nucleus-permeable, displaying almost complete dispersion of MBNL1 ribonuclear foci in a DM1 cell model. Direct evidence for the bioactivity of <b>9</b> was observed in its ability to disperse ribonuclear foci in individual live DM1 model cells using time-lapse confocal fluorescence microscopy

Developing Bivalent Ligands to Target CUG Triplet Repeats, the Causative Agent of Myotonic Dystrophy Type 1

An expanded CUG repeat transcript (CUG^exp) is the causative agent of myotonic dystrophy type 1 (DM1) by sequestering muscleblind-like 1 protein (MBNL1), a regulator of alternative splicing. On the basis of a ligand (<b>1</b>) that was previously reported to be active in an in vitro assay, we present the synthesis of a small library containing 10 dimeric ligands (<b>4</b>–<b>13</b>) that differ in length, composition, and attachment point of the linking chain. The oligoamino linkers gave a greater gain in affinity for CUG RNA and were more effective when compared to oligoether linkers. The most potent in vitro ligand (<b>9</b>) was shown to be aqueous-soluble and both cell- and nucleus-permeable, displaying almost complete dispersion of MBNL1 ribonuclear foci in a DM1 cell model. Direct evidence for the bioactivity of <b>9</b> was observed in its ability to disperse ribonuclear foci in individual live DM1 model cells using time-lapse confocal fluorescence microscopy

Developing Bivalent Ligands to Target CUG Triplet Repeats, the Causative Agent of Myotonic Dystrophy Type 1

An expanded CUG repeat transcript (CUG^exp) is the causative agent of myotonic dystrophy type 1 (DM1) by sequestering muscleblind-like 1 protein (MBNL1), a regulator of alternative splicing. On the basis of a ligand (<b>1</b>) that was previously reported to be active in an in vitro assay, we present the synthesis of a small library containing 10 dimeric ligands (<b>4</b>–<b>13</b>) that differ in length, composition, and attachment point of the linking chain. The oligoamino linkers gave a greater gain in affinity for CUG RNA and were more effective when compared to oligoether linkers. The most potent in vitro ligand (<b>9</b>) was shown to be aqueous-soluble and both cell- and nucleus-permeable, displaying almost complete dispersion of MBNL1 ribonuclear foci in a DM1 cell model. Direct evidence for the bioactivity of <b>9</b> was observed in its ability to disperse ribonuclear foci in individual live DM1 model cells using time-lapse confocal fluorescence microscopy

Substoichiometric Hydroxynonenylation of a Single Protein Recapitulates Whole-Cell-Stimulated Antioxidant Response

Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology

MOESM1 of Dissection of early transcriptional responses to water stress in Arundo donax L. by unigene-based RNA-seq

Additional file 1: Table S1. Experimental design, number of reads per library and sampling scheme

MOESM8 of Dissection of early transcriptional responses to water stress in Arundo donax L. by unigene-based RNA-seq

Additional file 8: Table S7. Comparison of co-regulated expression modules responsive to water stress in A. donax and rice

The genetic module BNB-GLID regulates germline fate determination in the liverwort Marchantia polymorpha

No description supplie