Soil labile organic carbon fractions and soil organic carbon stocks as affected by long-term organic and mineral fertilization regimes in the North ChinaPlain.

Background:Abnormalities within the insular cortex of the salience and thalamus of the hyperarousal network have been increasingly reported in healthy participants with insomnia symptoms by recent resting-state functional magnetic resonance imaging (rsfMRI) studies. However, little is known about the changes in functional interaction between the bilateral cerebral hemispheres in healthy participants with insomnia symptoms.Methods:In a randomized trial, 27 healthy participants with insomnia symptoms and 27 age-, gender-, and educational level-matched healthy participants without insomnia symptoms underwent rsfMRI. Voxel-mirrored homotopic connectivity (VMHC) was used to measure functional connectivity between any pair of symmetrical interhemispheric voxels (i.e., functional homotopy).Results:The healthy participants with insomnia symptoms displayed significantly increased VMHC compared to healthy participants without insomnia symptoms in the bilateral thalamus/posterior insula (including anterior insula), fusiform, middle cingulate gyrus, inferior parietal lobe, and postcentral gyrus. No regions of decreased VMHC were detected in healthy participants with insomnia symptoms. There were significantly positive correlations between the VMHC values in the anterior cingulate cortex (ACC) and sleep disturbance scores in all healthy participants.Conclusions:Insomnia is associated with substantial impairment of interhemispheric coordination within the default mode (ACC), salience (insula), hyperarousal (thalamus/posterior insula), and visual (fusiform) networks.

Fibrillary aggregates of amyloid-β (Aβ) are the pathological hallmark of Alzheimer’s disease (AD). Clearing Aβ deposition or inhibiting Aβ aggregation is a promising approach to treat AD. Experimental studies reported that dopamine (DA), an important neurotransmitter, can inhibit Aβ aggregation and disrupt Aβ fibrils in a dose-dependent manner. However, the underlying molecular mechanisms still remain mostly elusive. Herein, we investigated the effect of DA on Aβ42 protofibrils at three different DA-to-Aβ molar ratios (1:1, 2:1, and 10:1) using all-atom molecular dynamics simulations. Our simulations demonstrate that protonated DA at a DA-to-Aβ ratio of 2:1 exhibits stronger Aβ protofibril disruptive capacity than that at a molar-ratio of 1:1 by mostly disrupting the F4-L34-V36 hydrophobic core. When the ratio of DA-to-Aβ increases to 10:1, DA has a high probability to bind to the outer surface of protofibril and has negligible effect on the protofibril structure. Interestingly, at the same DA-to-Aβ ratio (10:1), a mixture of protonated (DA+) and deprotonated (DA0) DA molecules significantly disrupts Aβ protofibrils by the binding of DA0 to the F4-L34-V36 hydrophobic core. Replica-exchange molecular dynamics simulations of Aβ42 dimer show that DA+ inhibits the formation of β-sheets, K28-A42/K28-D23 salt-bridges, and interpeptide hydrophobic interactions and results in disordered coil-rich Aβ dimers, which would inhibit the subsequent fibrillization of Aβ. Further analyses reveal that DA disrupts Aβ protofibril and prevents Aβ dimerization mostly through π–π stacking interactions with residues F4, H6, and H13, hydrogen bonding interactions with negatively charged residues D7, E11, E22 and D23, and cation−π interactions with residues R5. This study provides a complete picture of the molecular mechanisms of DA in disrupting Aβ protofibril and inhibiting Aβ aggregation, which could be helpful for the design of potent drug candidates for the treatment/intervention of AD.

MiR-25 is a well-documented oncogenic miRNA implicated in esophageal squamous cell carcinoma (ESCC) development, progression and metastasis. However, whether and how miR-25 is involved in the development and metastasis of ESCC remain un-addressed. By using qRT-PCR analysis to compare levels of miR-25 in ESCC tissues with or without lymph node metastasis (LNM), it showed that ESCC tissues with LNM had increased levels of miR-25, which was correlated with tumor metastasis and poor prognosis. Gain-and loss-of-function assays indicated that targeting miR-25 could reverse EMT, and reduce in vitro cell migration and invasion, but not apoptosis and proliferation of ESCC. Furthermore, targeting miR-25 inhibited in vivo lung metastasis, and vice versa. And E-cadherin was a direct target of miR-25 through which affected EMT process and metastasis of ESCC. It is therefore indicated that miR-25 promotes metastasis of ESCC through E-cadherin and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of ESCC patients.

Patients with Alzheimer's disease (AD) have a high risk of developing Type II diabetes (T2D). The co-aggregation of the two disease-related proteins, Aβ and hIAPP, has been proposed as a potential molecular mechanism. However, the detailed Aβ−hIAPP interactions and structural characteristics of co-aggregates are mostly unknown at atomic level. Here, we explore the conformational ensembles of the Aβ−hIAPP heterodimer and Aβ or hIAPP homodimer by performing all-atom explicit-solvent replica exchange molecular dynamic simulations. Our simulations show that the interaction propensity of Aβ−hIAPP in the heterodimer is comparable with that of Aβ−Aβ/hIAPP−hIAPP in the homodimer. Similar hot spot residues of Aβ/hIAPP in the homodimer and heterodimer are identified, indicating that both Aβ and hIAPP have similar molecular recognition sites for self-aggregation and co-aggregation. Aβ in the heterodimer possesses three high β-sheet probability regions: the N-terminal region E3−H6, the central hydrophobic core region K16−E22, and the C-terminal hydrophobic region I31−A41, which is highly similar to Aβ in the homodimer. More importantly, in the heterodimer, the regions E3−H6, F19−E22, and I31−M35 of Aβ and the amyloid core region N20−T30 of hIAPP display higher β-sheet probability than they do in homodimer, implying their crucial roles in the formation of βsheet-rich co-aggregates. Our study sheds light on the co-aggregation of Aβ and hIAPP at an atomic level, which will be helpful for an in-depth understanding of the molecular mechanism for epidemiological correlation of AD and T2D.

Abnormal aggregation of proteins into pathological amyloid fibrils are implicated in a wide range of devastating human neurodegenerative diseases. Intracellular fibrillary inclusions formed by Tau protein are characterized as the...

Cancer mutations R175H and R273H induce p53C towards aggregation-prone conformations by increasing their SASA, water exposure of H-bonds and flexibility of loop2.

No abstract