Nucleosome Positioning and Its Role in Gene Regulation in Yeast

Nucleosome, composed of a 147-bp segment of DNA helix wrapped around a histone protein octamer, serves as the basic unit of chromatin. Nucleosome positioning refers to the relative position of DNA double helix with respect to the histone octamer. The positioning has an important role in transcription, DNA replication and other DNA transactions since packing DNA into nucleosomes occludes the binding site of proteins. Moreover, the nucleosomes bear histone modifications thus having a profound effect in regulation. Nucleosome positioning and its roles are extensively studied in model organism yeast. In this chapter, nucleosome organization and its roles in gene regulation are reviewed. Typically, nucleosomes are depleted around transcription start sites (TSSs), resulting in a nucleosome-free region (NFR) that is flanked by two well-positioned H2A.Z-containing nucleosomes. The nucleosomes downstream of the TSS are equally spaced in a nucleosome array. DNA sequences, especially 10–11 bp periodicities of some specific dinucleotides, partly determine the nucleosome positioning. Nucleosome occupancy can be determined with high throughput sequencing techniques. Importantly, nucleosome positions are dynamic in different cell types and different environments. Histones depletions, histones mutations, heat shock and changes in carbon source will profoundly change nucleosome organization. In the yeast cells, upon mutating the histones, the nucleosomes change drastically at promoters and the highly expressed genes, such as ribosome genes, undergo more change. The changes of nucleosomes tightly associate the transcription initiation, elongation and termination. H2A.Z is contained in the +1 and −1 nucleosomes and thus in transcription. Chaperon Chz1 and elongation factor Spt16 function in H2A.Z deposition on chromatin. The chapter covers the basic concept of nucleosomes, nucleosome determinant, the techniques of mapping nucleosomes, nucleosome alteration upon stress and mutation, and Htz1 dynamics on chromatin

Numerical Study of the Movement of Fine Particle in Sound Wave Field

AbstractInhalable particulate matter, especially PM2.5 is one of the main pollutants in China and it's harmful to both human health and atmosphere. Since the removal efficiency of traditional dust removal devices such as ESP for PM2.5 is very low, pretreatment becomes necessary before the dust gets into the dust remover. Acoustic agglomeration is one of the pretreatment technologies which uses sound wave with high intensity to make fine particles get agglomerate and grow up, and improves the efficiency of traditional dust removal devices for PM2.5. In sound wave field, fine particles are carried by the medium which in this paper is air, and vibrate with different amplitude because of different particle sizes, thus relative movement appears and then particles have more chances to collide and get agglomerate. In this paper, the movement of particles with different sizes in travelling wave sound field and standing wave sound field were calculated, including the velocity, displacement, amplitude and so on. The situation that Re<1 was considered and Viscous force in Stokes region was chose as the main forces here. Studying the movement of fine particle in sound field with different conditions has great meaning in learning the mechanisms of acoustic agglomeration

Mushroom polysaccharides with potential in anti-diabetes: Biological mechanisms, extraction, and future perspectives: A review

Diabetes mellitus (DM) is a global health threat. Searching for anti-diabetic components from natural resources is of intense interest to scientists. Mushroom polysaccharides have received growing attention in anti-diabetes fields due to their advantages in broad resources, structure diversity, and multiple bioactivities, which are considered an unlimited source of healthy active components potentially applied in functional foods and nutraceuticals. In this review, the current knowledge about the roles of oxidative stress in the pathogenesis of DM, the extraction method of mushroom polysaccharides, and their potential biological mechanisms associated with anti-diabetes, including antioxidant, hypolipidemic, anti-inflammatory, and gut microbiota modulatory actions, were summarized based on a variety of in vitro and in vivo studies, with aiming at better understanding the roles of mushroom polysaccharides in the prevention and management of DM and its complications. Finally, future perspectives including bridging the gap between the intervention of mushroom polysaccharides and the modulation of insulin signaling pathway, revealing structure-bioactivity of mushroom polysaccharides, developing synergistic foods, conducting well-controlled clinical trials that may be very helpful in discovering valuable mushroom polysaccharides and better applications of mushroom polysaccharides in diabetic control were proposed

Dispersive Liquid-Liquid Microextraction Combined with Ultrahigh Performance Liquid Chromatography/Tandem Mass Spectrometry for Determination of Organophosphate Esters in Aqueous Samples

A new technique was established to identify eight organophosphate esters (OPEs) in this work. It utilised dispersive liquid-liquid microextraction in combination with ultrahigh performance liquid chromatography/tandem mass spectrometry. The type and volume of extraction solvents, dispersion agent, and amount of NaCl were optimized. The target analytes were detected in the range of 1.0–200 µg/L with correlation coefficients ranging from 0.9982 to 0.9998, and the detection limits of the analytes were ranged from 0.02 to 0.07 µg/L (S/N=3). The feasibility of this method was demonstrated by identifying OPEs in aqueous samples that exhibited spiked recoveries, which ranged between 48.7% and 58.3% for triethyl phosphate (TEP) as well as between 85.9% and 113% for the other OPEs. The precision was ranged from 3.2% to 9.3% (n=6), and the interprecision was ranged from 2.6% to 12.3% (n=5). Only 2 of the 12 selected samples were tested to be positive for OPEs, and the total concentrations of OPEs in them were 1.1 and 1.6 µg/L, respectively. This method was confirmed to be simple, fast, and accurate for identifying OPEs in aqueous samples

T cell antigen discovery via trogocytosis

T cell receptor (TCR) ligand discovery is essential for understanding and manipulating immune responses to tumors. We developed a cell-based selection platform for TCR ligand discovery that exploits a membrane transfer phenomenon called trogocytosis. We discovered that T cell membrane proteins are transferred specifically to target cells that present cognate peptide–major histocompatibility complex (MHC) molecules. Co-incubation of T cells expressing an orphan TCR with target cells collectively presenting a library of peptide–MHCs led to specific labeling of cognate target cells, enabling isolation of these target cells and sequencing of the cognate TCR ligand. We validated this method for two clinically employed TCRs and further used the platform to identify the cognate neoepitope for a subject-derived neoantigen-specific TCR. Thus, target cell trogocytosis is a robust tool for TCR ligand discovery that will be useful for studying basic tumor immunology and identifying new targets for immunotherapy

Homer1a Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Stress After Ischemic Reperfusion Injury by Inhibiting the PERK Pathway

Homer1a is the short form of a scaffold protein that plays a protective role in many forms of stress. However, the role of Homer1a in cerebral ischemia/reperfusion (I/R) injury and its potential mechanism is still unknown. In this study, we found that Homer1a was upregulated by oxygen and glucose deprivation (OGD) and that overexpression of Homer1a alleviated OGD-induced lactate dehydrogenase (LDH) release and cell death in cultured cortical neurons. After OGD treatment, the overexpression of Homer1a preserved mitochondrial function, as evidenced by less cytochrome c release, less reactive oxygen species (ROS) production, less ATP and mitochondrial membrane potential (MMP) loss, less caspase-9 activation, and inhibition of endoplasmic reticulum (ER) stress confirmed by the decreased expression of phosphate-PKR-like ER Kinase (p-PERK)/PERK and phosphate- inositol-requiring enzyme 1 (p-IRE1)/IRE1 and immunofluorescence (IF) staining. In addition, mitochondrial protection of Homer1a was blocked by the ER stress activator Tunicamycin (TM) with a re-escalated ROS level, increasing ATP and MMP loss. Furthermore, Homer1a overexpression-induced mitochondrial stress attenuation was significantly reversed by activating the PERK pathway with TM and p-IRE1 inhibitor 3,5-dibromosalicylaldehyde (DBSA), as evidenced by increased cytochrome c release, increased ATP loss and a higher ROS level. However, activating the IRE1 pathway with TM and p-PERK inhibitor GSK2656157 showed little change in cytochrome c release and exhibited a moderate upgrade of ATP loss and ROS production in neurons. In summary, these findings demonstrated that Homer1a protects against OGD-induced injury by preserving mitochondrial function through inhibiting the PERK pathway. Our finding may reveal a promising target of protecting neurons from cerebral I/R injury

HETDEX pilot survey for emission-line galaxies - I. Survey design, performance, and catalog

We present a catalog of emission-line galaxies selected solely by their emission-line fluxes using a wide-field integral field spectrograph. This work is partially motivated as a pilot survey for the upcoming Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). We describe the observations, reductions, detections, redshift classifications, line fluxes, and counterpart information for 397 emission-line galaxies detected over 169 sq.arcmin with a 3500-5800 Ang. bandpass under 5 Ang. full-width-half-maximum (FWHM) spectral resolution. The survey's best sensitivity for unresolved objects under photometric conditions is between 4-20 E-17 erg/s/sq.cm depending on the wavelength, and Ly-alpha luminosities between 3-6 E42 erg/s are detectable. This survey method complements narrowband and color-selection techniques in the search for high redshift galaxies with its different selection properties and large volume probed. The four survey fields within the COSMOS, GOODS-N, MUNICS, and XMM-LSS areas are rich with existing, complementary data. We find 104 galaxies via their high redshift Ly-alpha emission at 1.9<z<3.8, and the majority of the remainder objects are low redshift [OII]3727 emitters at z<0.56. The classification between low and high redshift objects depends on rest frame equivalent width, as well as other indicators, where available. Based on matches to X-ray catalogs, the active galactic nuclei (AGN) fraction amongst the Ly-alpha emitters (LAEs) is 6%. We also analyze the survey's completeness and contamination properties through simulations. We find five high-z, highly-significant, resolved objects with full-width-half-maximum sizes >44 sq.arcsec which appear to be extended Ly-alpha nebulae. We also find three high-z objects with rest frame Ly-alpha equivalent widths above the level believed to be achievable with normal star formation, EW(rest)>240 Ang.Comment: 45 pages, 36 figures, 5 tables, submitted to ApJ

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL