Barrett’s Esophagus and Intestinal Metaplasia

Intestinal metaplasia refers to the replacement of the differentiated and mature normal mucosal epithelium outside the intestinal tract by the intestinal epithelium. This paper briefly describes the etiology and clinical significance of intestinal metaplasia in Barrett’s esophagus. This article summarizes the impact of intestinal metaplasia on the diagnosis, monitoring, and treatment of Barrett’s esophagus according to different guidelines. We also briefly explore the basis for the endoscopic diagnosis of intestinal metaplasia in Barrett’s esophagus. The identification techniques of goblet cells in Barrett’s esophagus are also elucidated by some scholars. Additionally, we further elaborate on the current treatment methods related to Barrett’s esophagus

Tumor Cell Phenotype Is Sustained by Selective MAPK Oxidation in Mitochondria

Mitochondria are major cellular sources of hydrogen peroxide (H2O2), the production of which is modulated by oxygen availability and the mitochondrial energy state. An increase of steady-state cell H2O2 concentration is able to control the transition from proliferating to quiescent phenotypes and to signal the end of proliferation; in tumor cells thereby, low H2O2 due to defective mitochondrial metabolism can contribute to sustain proliferation. Mitogen-activated protein kinases (MAPKs) orchestrate signal transduction and recent data indicate that are present in mitochondria and regulated by the redox state. On these bases, we investigated the mechanistic connection of tumor mitochondrial dysfunction, H2O2 yield, and activation of MAPKs in LP07 murine tumor cells with confocal microscopy, in vivo imaging and directed mutagenesis. Two redox conditions were examined: low 1 µM H2O2 increased cell proliferation in ERK1/2-dependent manner whereas high 50 µM H2O2 arrested cell cycle by p38 and JNK1/2 activation. Regarding the experimental conditions as a three-compartment model (mitochondria, cytosol, and nuclei), the different responses depended on MAPKs preferential traffic to mitochondria, where a selective activation of either ERK1/2 or p38-JNK1/2 by co-localized upstream kinases (MAPKKs) facilitated their further passage to nuclei. As assessed by mass spectra, MAPKs activation and efficient binding to cognate MAPKKs resulted from oxidation of conserved ERK1/2 or p38-JNK1/2 cysteine domains to sulfinic and sulfonic acids at a definite H2O2 level. Like this, high H2O2 or directed mutation of redox-sensitive ERK2 Cys214 impeded binding to MEK1/2, caused ERK2 retention in mitochondria and restricted shuttle to nuclei. It is surmised that selective cysteine oxidations adjust the electrostatic forces that participate in a particular MAPK-MAPKK interaction. Considering that tumor mitochondria are dysfunctional, their inability to increase H2O2 yield should disrupt synchronized MAPK oxidations and the regulation of cell cycle leading cells to remain in a proliferating phenotype

Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration

Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally expanded polyglutamine tract. A total of nine polyQ disorders have been identified, including Huntington\u27s disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). The diseases of this class are each considered rare, yet polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. While each subtype of polyQ diseases has its own causative gene, certain pathologic molecular attributes have been implicated in virtually all of the polyQ diseases, including protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, and mitochondrial dysfunction. Although animal models of polyQ disease are available helping to understand their pathogenesis and access disease-modifying therapies, there is neither a cure nor prevention for these diseases, with only symptomatic treatments available. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in the class of polyQ diseases. We examine the publication landscape in the area in effort to provide insights into current knowledge advances and developments. We review the most discussed concepts and assess the strategies to combat these diseases. Finally, we inspect clinical applications of products against polyQ diseases with their development pipelines. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding the class of polyQ diseases, to outline challenges, and evaluate growth opportunities to further efforts in combating the diseases

The Mechanical Properties of Granite under Ultrasonic Vibration

The new technique of using ultrasonic vibration to break hard rock is still in the experimental stage, but it has significant potential for improving the efficiency of hard rock crushing. We have analyzed the mechanical properties of granite under ultrasonic vibration and the characteristics of the damage produced. This was achieved by using an ultraloading device to apply continuous and discontinuous ultrasonic vibrations, respectively, to 32 mm diameter and 72 mm high granite samples. An ultradynamic data acceptor combined with strain gauges was used to monitor the strain of the granite in real time, and the elastic-plastic deformation behavior of the granite under ultrasonic vibration was observed. The results of this experiment indicate that the granite samples underwent elastic deformation, plastic deformation, and damage during this process. The samples first experienced compressive deformation with no obvious rupturing. As the vibration continued, the deformation finally became tensile, and significant fragmentation occurred. The mechanical properties of granite under ultrasonic vibration are analyzed in detail on the basis of these results, and the basis for selecting a vibration frequency is discussed

A P2P Communication Model for IPv4/IPv6 Hybrid Network

We propose a P2P based communication model to resolve the inter-communication problem among the IPv4 and IPv6 terminals in large scale system. Our model well captures the traversing requirement of such hybrid network and achieves a balanced load through the networks. In addition, the model is highly adaptable to network topology changes and is able to support mobile terminals communication. We present the routing mechanism based on a route locality and searching algorithm built on Distributed Hash Table (DHT). The terminals form a flexible Overlay Network where each device has a unique Peer ID. They serve as a ¡ skeleton ¡ of the network and distributedly store the route information and the mapping between IP addresses and Peer IDs. Our method provides both a seamless communication for the current hybrid network and a painless switching from IPv4 to IPv6. 1

Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging

AbstractMitochondrial dysfunction is often associated with aging and neurodegeneration. c-Jun-N-terminal kinase (JNK) phosphorylation and its translocation to mitochondria increased as a function of age in rat brain. This was associated with a decrease of pyruvate dehydrogenase (PDH) activity upon phosphorylation of the E1α subunit of PDH. Phosphorylation of PDH is likely mediated by PDH kinase, the protein levels and activity of which increased with age. ATP levels were diminished, whereas lactic acid levels increased, thus indicating a shift toward anaerobic glycolysis. The energy transduction deficit due to impairment of PDH activity during aging may be associated with JNK signaling

An RNA-binding protein, RNP-1, protects microtubules from nocodazole and localizes to the leading edge during cytokinesis and cell migration in Dictyostelium cells

Aim: RNA-binding proteins are a large group of regulators (800-1000 in humans), some of which play significant roles in mRN A local translation. In this study, we analyzed the functions of the protein RNP-1, which was previously discovered in a genetic selection screen for nocodazole suppression. Methods: The growth rates and the microtubule networks of Dictyostelium cells were assessed with or without nocodazole (10 μmol/L) in suspension culture. Fluorescent images of RNP-1-GFP and RFP-tubulin were captured when cells were undergoing cytokinesis, then the GFP signal intensity and distance to the nearest centrosome were analyzed by using a computer program written in Matlab ®. The RNP-1-GFP-expresseding cells were polarized, and the time-lapse images of cells were captured when cells were chemotaxing to a cAMP source. Results: Over-expression of RNP-1 rescued the growth defects caused by the microtubule-destabilizing agent nocodazole. Over-expression of RNP-1 protected microtubules from nocodazole treatment. In cells undergoing cytokinesis, the RNP-1 protein was localized to the polar regions of the cell cortex, and protein levels decreased proportionally as the power of the distance from the cell cortex to the nearest centrosome. In chemotactic cells, the RNP-1 protein localized to the leading edge of moving cells. Sequence analysis revealed that RNP-1 has two RNA-binding domains and is related to cytosolic poly(A)-binding proteins (PABPCs) in humans. Conclusion: RNP-1 has roles in protecting microtubules and in directing cortical movement during cytokinesis and cell migration in Dictyostelium cells. The sequence similarity of RNP-1 to human PABPCs suggests that PABPCs may have similar functions in mammalian cells, perhaps in regulating microtubule dynamics and functions during cortical movement in cytokinesis and cell migration