Mechanisms of Epithelial-Mesenchymal Transition of Peritoneal Mesothelial Cells During Peritoneal Dialysis

A growing body of evidence indicates that epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMC) may play an important role in the development and progression of peritoneal fibrosis during long-term peritoneal dialysis (PD) leading to failure of peritoneal membrane function. Here, we review our own observations and those of others on the mechanisms of EMT of HPMC and suggest potential therapeutic strategies to prevent EMT and peritoneal fibrosis during long-term PD. We found that high glucose and H2O2 as well as transforming growth factor-β1 (TGF-β1) induced EMT in HPMC and that high glucose-induced EMT was blocked not only by inhibition of TGF-β1 but also by antioxidants or inhibitors of mitogen-activated protein kinases (MAPK). Since MAPKs are downstream target molecules of reactive oxygen species (ROS), these data suggest that high glucose-induced generation of ROS and subsequent MAPK activation mediate high glucose-induced EMT in HPMC. We and others also observed that bone morphogenetic protein-7 (BMP-7) prevented EMT in HPMC. Glucose degradation products (GDP) were shown to play a role in inducing EMT. Involvement of a mammalian target of rapamycin (mTOR) in TGF-β1-induced EMT has also been proposed in cultured HPMC. A better understanding of the precise mechanisms involved in EMT of HPMC may provide new therapeutic strategies for inhibiting peritoneal fibrosis in long-term PD patients

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Tuning of Riboswitch-Based Genetic Devices to Have Desired Dose-Reponse Curves

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Host–Guest Chemistry in the Gas Phase: Complex Formation of Cucurbit[6]uril with Proton-bound Water Dimer

The hydration of cucurbit[6]uril (CB[6]) in the gas phase is investigated using electrospray ionization traveling wave ion mobility mass spectrometry (ESI-TWIM-MS). Highly abundant dihydrated and tetrahydrated species of diprotonated CB[6] are found in the ESI-TWIM-MS spectrum. The hydration patterns of the CB[6] ion and the dissociation patterns of the hydrated CB[6] ion indicate that two water molecules are bound to each other, forming a water dimer in the CB[6] complex. Ion mobility studies combined with the structures calculated by density functional theory suggest that the proton-bound water dimer is present as a Zundel-like structure in the CB[6] portal, forming a hydrogen bond network with carbonyl groups of the CB[6]. When a large guest molecule is bound to a CB[6] portal, water molecules cannot bind to the portal. In addition, the strong binding energy of the water dimer blocks the portal, hindering the insertion of the long alkyl chain of the guest molecule into the CB[6] cavity. With small alkali metal cations, such as Li+ and Na+, a single water molecule interacts with the CB[6] portal, forming hydrogen bonds with the carbonyl groups of CB[6]. A highly stable Zundel-like structure of the proton-bound water dimer or a metal-bound water molecule at the CB[6] portal is suggested as an initial hydration process for CB[6], which is only dissolved in aqueous solution with acid or alkali metal ions.X1197sciescopu

Tuning the coenzyme B 12 riboswitch sensor with a transcriptional repressor to invert and amplify the signal

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Development of Coenzyme B12 Sensor by Using Riboswitch and Transcriptional Repressor for Signal Tuning

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Diffractive X‑ray Waveguiding Reveals Orthogonal Crystalline Stratification in Conjugated Polymer Thin Films

The depth dependence of crystalline structure within thin films is critical for many technological applications but has been impossible to measure directly using common techniques. In this work, by monitoring diffraction peak intensity and location and utilizing the highly angle-dependent waveguiding effects of X-rays near grazing incidence, we quantitatively measure the thickness, roughness, and orientation of stratified crystalline layers within thin films of a high-performance semiconducting polymer. In particular, this diffractive X-ray waveguiding reveals a self-organized 5 nm thick crystalline surface layer with crystalline orientation orthogonal to the underlying 65 nm thick layer. While demonstrated for an organic semiconductor film, this approach is applicable to any thin film material system with stratified crystalline structure where orientation can influence important interfacial processes such as charge injection and field-effect transport