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1
Neubauer, Olivia, Anja Alfandega, Janna Schoknecht, Ulrich Sternberg, Anne Pohlmann e Thomas Eitinger. "Two Essential Arginine Residues in the T Components of Energy-Coupling Factor Transporters". Journal of Bacteriology 191, n. 21 (28 agosto 2009): 6482–88. http://dx.doi.org/10.1128/jb.00965-09.
Abstract (sommario):
ABSTRACT Energy-coupling factor (ECF) transporters, a recently discovered class of importers of micronutrients, are composed of a substrate-specific transmembrane component (S component) and a conserved energy-coupling module consisting of a transmembrane protein (T component) and pairs of ABC ATPases (A proteins). Based on utilization of a dedicated (subclass I) or shared (subclass II) energy-coupling module, ECF systems fall into two subclasses. The T components are the least-characterized proteins of ECF importers, and their function is essentially unknown. Using RcBioN and LmEcfT, the T units of the subclass I biotin transporter (RcBioMNY) of a gram-negative bacterium and of the subclass II folate, pantothenate, and riboflavin transporters of a lactic acid bacterium, respectively, we analyzed the role of two strongly conserved short motifs, each containing an arginine residue. Individual replacement of the two Arg residues in RcBioN reduced ATPase activity, an indicator of the transporter function, by two-thirds without affecting the modular assembly of the RcBioMNY complex. A double Arg-to-Glu replacement destroyed the complex and abolished ATPase activity. The corresponding single mutation in motif II of LmEcfT, as well as a double mutation, led to loss of the T unit from the subclass II ECF transporters and inactivated these systems. A single Arg-to-Glu replacement in motif I, however, abolished vitamin uptake activity without affecting assembly of the modules. Our results indicate that the conserved motif I in T components is essential for intramolecular signaling and, in cooperation with motif II, for subunit assembly of modular ECF transporters.
2
Comelli, Raúl N., Elina Welchen, Hye Jin Kim, Jong Chan Hong e Daniel H. Gonzalez. "Delta subclass HD-Zip proteins and a B-3 AP2/ERF transcription factor interact with promoter elements required for expression of the Arabidopsis cytochrome c oxidase 5b-1 gene". Plant Molecular Biology 80, n. 2 (6 giugno 2012): 157–67. http://dx.doi.org/10.1007/s11103-012-9935-9.
3
Mounteer, Ann H., Flávia ML Passos, Arnaldo Chaer Borges e Daison Olzany Silva. "Detecting structural and functional differences in activated sludge bacterial communities originating from laboratory treatment of elementally and totally chlorine-free bleaching effluents". Canadian Journal of Microbiology 48, n. 3 (1 marzo 2002): 245–55. http://dx.doi.org/10.1139/w02-006.
Abstract (sommario):
The ability to differentiate functional and structural diversity of bacterial communities present in activated sludges adapted to elementally (ECF) and totally (TCF) chlorine-free bleaching effluents was evaluated. Community function was evaluated through substrate utilization patterns in BiologGN®microplates, and taxonomic structure was evaluated by fluorescent in situ hybridization using probes targeting the Eubacteria; the alpha, beta, and gamma subclasses of the Proteobacteria; and gram-positive bacteria with high GC content. Over 6-week sampling periods, ECF- and TCF-adapted sludge bacterial communities presented reproducible substrate utilization patterns that through principal components (PCs) analysis, separated the ECF samples from the TCF samples. Application of the fluorescent in situ hybridization technique was complicated by the intense autofluorescence of the bleaching effluent sludge samples that interfered with detection of specific hybridization signals. The most notable difference in community structure detected using the chosen set of probes was the relatively greater proportion of cells of the alpha subclass in TCF sludge (27%) than in ECF sludge (6%). Nonspecific hybridization with beta and gamma probes was relatively high, but both sludges appeared to have similar proportions of cells of the beta (2022%) and gamma (1112%) subclasses. The two sludges presented relatively few gram-positive cells with high GC content (<0.2% of eubacterial counts). Differences in both metabolic potential and taxonomic structure of the microbial communities in the ECF- and TCF-activated sludges were detected. The kinetics of the development of these differences in treatment plants and their relationships with treatment efficiency and production process conditions should now be evaluated.Key words: activated sludge, bleaching effluents, Biolog, in situ hybridization.
4
Defize, L. H., J. Boonstra, J. Meisenhelder, W. Kruijer, L. G. Tertoolen, B. C. Tilly, T. Hunter, P. M. van Bergen en Henegouwen, W. H. Moolenaar e S. W. de Laat. "Signal transduction by epidermal growth factor occurs through the subclass of high affinity receptors." Journal of Cell Biology 109, n. 5 (1 novembre 1989): 2495–507. http://dx.doi.org/10.1083/jcb.109.5.2495.
Abstract (sommario):
Many cell types display two classes of epidermal growth factor receptor (EGFR) as judged from EGF binding studies; i.e., a major class of low affinity EGFR and a minor class of high affinity EGFR. We have studied their respective contribution to the cascade of events elicited by EGF in human A431 carcinoma cells, using anti-EGFR mAb 2E9. This antibody specifically blocks EGF binding to low affinity EGFR, without activating receptors in intact cells, and thus enables us to study the effects of exclusive EGF binding to high affinity EGFR. We show that blocking of low affinity EGFR by mAb 2E9 has almost no effect on the activation of the receptor protein-tyrosine kinase by EGF, suggesting that EGFR kinase activation occurs exclusively through the subclass of high affinity EGFR (5-10%). In addition, we provide evidence that high affinity EGFR exists both in monomeric and dimeric forms, and that cross-phosphorylation of low affinity EGFR by high affinity EGFR may take place in dimers of both receptor types. We demonstrate that the following early cellular response to EGF are also unimpaired in the presence of mAb 2E9: (a) inositol phosphate production, (b) release of Ca2+ from intracellular stores, (c) rise in intracellular pH, (d) phosphorylation of EGF on threonine residue 654, (e) induction of c-fos gene expression, and (f) alteration in cell morphology. As possible nonspecific side effects, we observed that the EGF induced Ca2+ influx and fluid-phase pinocytosis were inhibited in A431 cells in the presence of mAb 2E9. We conclude, therefore, that the activation of the EGFR signal transduction cascade can occur completely through exclusive binding of EGF to the subclass of high affinity EGFR.
5
Defize, L. H., D. J. Arndt-Jovin, T. M. Jovin, J. Boonstra, J. Meisenhelder, T. Hunter, H. T. de Hey e S. W. de Laat. "A431 cell variants lacking the blood group A antigen display increased high affinity epidermal growth factor-receptor number, protein-tyrosine kinase activity, and receptor turnover." Journal of Cell Biology 107, n. 3 (1 settembre 1988): 939–49. http://dx.doi.org/10.1083/jcb.107.3.939.
Abstract (sommario):
The epidermal growth factor receptor (EGF-R) of human A431 cells bears an antigenic determinant that is closely related to the human blood group A carbohydrate structure. Labeling studies with blood group A reactive anti-EGF-R monoclonal antibodies and various lectins revealed that A431 cultures are heterogeneous with respect to blood group A expression. We have isolated clonal variants of these cells that either express (A431A+ cells) or completely lack (A431A- cells) the blood group A specific N-acetyl-D-galactosamine (GalNAc) residue. We show that this difference is due to the absence of a UDP-GalNAc:Gal transferase activity in A431A- cells. Subsequently, we have compared EGF-R functioning in these cell lines. Scatchard analysis of EGF-binding shows that in A431A- cells 6.3% of the EGF-R belongs to a high affinity subclass (Kd = 0.4 nM) while in A431A+ this subclass represents only 3.2% of the total receptor pool. The elevated level of high affinity receptors in A431A- cells is accompanied by a parallel increase in receptor protein- tyrosine kinase activity. In membrane preparations of A431A- cells, receptor autophosphorylation as well as phosphorylation of a tyrosine-containing peptide substrate is 2-3-fold higher as compared with A431A+ cells. In intact A431A-cells, the difference in receptor activity is measured as a 2-3-fold elevated level of receptor phosphorylation and a 2-3-fold higher abundance of phosphotyrosine in total cellular protein in A431A- cells. In addition, [35S]methionine pulse-chase experiments showed a ligand-independent increase in turnover of EGF-R in A431A- cells: the receptor's half life in these cells is 10 h as compared with 17 h in A431A+ cells. Our results suggest a possible involvement of GalNAc residue(s) in determining EGF-R affinity, protein-tyrosine kinase activity and turnover in A431 cells. Furthermore, our results indicate that high affinity EGF-R are the biologically active species with respect to protein-tyrosine kinase activity.
6
Kilic, Mukremin, Pierre Bergeron, Simon Blouin, Gracyn Jewett, Warren R. Brown e Adam Moss. "White Dwarf Merger Remnants: The DAQ Subclass". Astrophysical Journal 965, n. 2 (1 aprile 2024): 159. http://dx.doi.org/10.3847/1538-4357/ad3440.
Abstract (sommario):
Abstract Four years after the discovery of a unique DAQ white dwarf with a hydrogen-dominated and carbon-rich atmosphere, we report the discovery of four new DAQ white dwarfs, including two that were not recognized properly in the literature. We find all five DAQs in a relatively narrow mass and temperature range of M = 1.14–1.19 M ⊙ and T eff = 13,000–17,000 K. In addition, at least two show photometric variations due to rapid rotation with ≈10 minute periods. All five are also kinematically old, but appear photometrically young, with estimated cooling ages of about 1 Gyr based on standard cooling tracks, and their masses are roughly twice the mass of the most common white dwarfs in the solar neighborhood. These characteristics are smoking gun signatures of white dwarf merger remnants. Comparing the DAQ sample with warm DQ white dwarfs, we demonstrate that there is a range of hydrogen abundances among the warm DQ population and that the distinction between DAQ and warm DQ white dwarfs is superficial. We discuss the potential evolutionary channels for the emergence of the DAQ subclass, suggesting that DAQ white dwarfs are trapped on the crystallization sequence and may remain there for a significant fraction of the Hubble time.
7
Li, Yan, e Yaqiang Wang. "Some new results for $ B_1 $-matrices". Electronic Research Archive 31, n. 8 (2023): 4773–87. http://dx.doi.org/10.3934/era.2023244.
Abstract (sommario):
<abstract><p>The class of $ B_1 $-matrices is a subclass of $ P $-matrices and introduced as a generalization of $ B $-matrices. In this paper, we present several properties for $ B_1 $-matrices. Then, the infinity norm upper bound for the inverse of $ B_1 $-matrices is obtained. Furthermore, the error bound for the linear complementarity problem of $ B_1 $-matrices is presented. Finally, some numerical examples are given to illustrate our results.</p></abstract>
8
Qi, Jiaqi, e Yaqiang Wang. "Subdirect Sums of $ GSD{D_1} $ matrices". Electronic Research Archive 32, n. 6 (2024): 3989–4010. http://dx.doi.org/10.3934/era.2024179.
Abstract (sommario):
<abstract><p>The class of generalized $ SD{D_1} \; \left({GSD{D_1}} \right) $ matrices is a new subclass of $ H $-matrices. In this paper, we focus on the subdirect sum of $ GSD{D_1} $ matrices, and some sufficient conditions to ensure that the subdirect sum of $ GSD{D_1} $ matrices with strictly diagonally dominant $ \left({SDD} \right) $ matrices is in the class of $ GSD{D_1} $ matrices are given. Moreover, corresponding examples are given to illustrate our results.</p></abstract>
9
Liu, Yi, Lei Gao e Tianxu Zhao. "Partially doubly strictly diagonally dominant matrices with applications". Electronic Research Archive 31, n. 5 (2023): 2994–3013. http://dx.doi.org/10.3934/era.2023151.
Abstract (sommario):
<abstract><p>A new class of matrices called partially doubly strictly diagonally dominant (for shortly, PDSDD) matrices is introduced and proved to be a subclass of nonsingular $ H $-matrices, which generalizes doubly strictly diagonally dominant matrices. As applications, a new eigenvalue localization set for matrices is given, and an upper bound for the infinity norm bound of the inverse of PDSDD matrices is presented. Based on this bound, a new pseudospectra localization for matrices is derived and a lower bound for distance to instability is obtained.</p></abstract>
10
Merchant, J. L., G. R. Iyer, B. R. Taylor, J. R. Kitchen, E. R. Mortensen, Z. Wang, R. J. Flintoft, J. B. Michel e R. Bassel-Duby. "ZBP-89, a Krüppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter." Molecular and Cellular Biology 16, n. 12 (dicembre 1996): 6644–53. http://dx.doi.org/10.1128/mcb.16.12.6644.
Abstract (sommario):
We have shown previously that a GC-rich element (GGGGCGGGGTGGGGGG) conferring epidermal growth factor (EGF) responsiveness to the human gastrin promoter binds Sp1 and additional undefined complexes. A rat GH4 cell line expression library was screened by using a multimer of the gastrin EGF response element, and three overlapping cDNA clones were identified. The full-length rat cDNA encoded an 89-kDa zinc finger protein (ZBP-89) that was 89% identical to a 49-kDa human factor, ht(beta), that binds a GTGGG/CACCC element in T-cell receptor promoters. The conservation of amino acids between the zinc fingers indicates that ZBP-89 is a member of the C2H2 zinc finger family subclass typified by the Drosophila Krüppel protein. ZBP-89 is ubiquitously expressed in normal adult tissues. It binds specifically to the gastrin EGF response element and inhibits EGF induction of the gastrin promoter. Collectively, these results demonstrate that ZBP-89 functions as a repressor of basal and inducible expression of the gastrin gene.
11
Timmers, Cynthia, Nidhi Sharma, Rene Opavsky, Baidehi Maiti, Lizhao Wu, Juan Wu, Daniel Orringer, Prashant Trikha, Harold I. Saavedra e Gustavo Leone. "E2f1, E2f2, and E2f3 Control E2F Target Expression and Cellular Proliferation via a p53-Dependent Negative Feedback Loop". Molecular and Cellular Biology 27, n. 1 (1 gennaio 2007): 65–78. http://dx.doi.org/10.1128/mcb.02147-05.
Abstract (sommario):
ABSTRACT E2F-mediated control of gene expression is believed to have an essential role in the control of cellular proliferation. Using a conditional gene-targeting approach, we show that the targeted disruption of the entire E2F activator subclass composed of E2f1, E2f2, and E2f3 in mouse embryonic fibroblasts leads to the activation of p53 and the induction of p53 target genes, including p21 CIP1 . Consequently, cyclin-dependent kinase activity and retinoblastoma (Rb) phosphorylation are dramatically inhibited, leading to Rb/E2F-mediated repression of E2F target gene expression and a severe block in cellular proliferation. Inactivation of p53 in E2f1-, E2f2-, and E2f3-deficient cells, either by spontaneous mutation or by conditional gene ablation, prevented the induction of p21 CIP1 and many other p53 target genes. As a result, cyclin-dependent kinase activity, Rb phosphorylation, and E2F target gene expression were restored to nearly normal levels, rendering cells responsive to normal growth signals. These findings suggest that a critical function of the E2F1, E2F2, and E2F3 activators is in the control of a p53-dependent axis that indirectly regulates E2F-mediated transcriptional repression and cellular proliferation.
12
Dong, Jianying, Lee K. Opresko, William Chrisler, Galya Orr, Ryan D. Quesenberry, Douglas A. Lauffenburger e H. Steven Wiley. "The Membrane-anchoring Domain of Epidermal Growth Factor Receptor Ligands Dictates Their Ability to Operate in Juxtacrine Mode". Molecular Biology of the Cell 16, n. 6 (giugno 2005): 2984–98. http://dx.doi.org/10.1091/mbc.e04-11-0994.
Abstract (sommario):
All ligands of the epidermal growth factor (EGF) receptor (EGFR) are synthesized as membrane-anchored precursors. Previous work has suggested that some ligands, such as EGF, must be proteolytically released to be active, whereas others, such as heparin-binding EGF-like growth factor (HB-EGF) can function while still anchored to the membrane (i.e., juxtacrine signaling). To explore the structural basis for these differences in ligand activity, we engineered a series of membrane-anchored ligands in which the core, receptor-binding domain of EGF was combined with different domains of both EGF and HB-EGF. We found that ligands having the N-terminal extension of EGF could not bind to the EGFR, even when released from the membrane. Ligands lacking an N-terminal extension, but possessing the membrane-anchoring domain of EGF, still required proteolytic release for activity, whereas ligands with the membrane-anchoring domain of HB-EGF could elicit full biological activity while still membrane anchored. Ligands containing the HB-EGF membrane anchor, but lacking an N-terminal extension, activated EGFR during their transit through the Golgi apparatus. However, cell-mixing experiments and fluorescence resonance energy transfer studies showed that juxtacrine signaling typically occurred in trans at the cell surface, at points of cell-cell contact. Our data suggest that the membrane-anchoring domain of ligands selectively controls their ability to participate in juxtacrine signaling and thus, only a subclass of EGFR ligands can act in a juxtacrine mode.
13
Chen, Xi, Xuemei He, Jian Sun e Zhenxing Wang. "Phytochemical Composition, Antioxidant Activity, α-Glucosidase and Acetylcholinesterase Inhibitory Activity of Quinoa Extract and Its Fractions". Molecules 27, n. 8 (8 aprile 2022): 2420. http://dx.doi.org/10.3390/molecules27082420.
Abstract (sommario):
This study is aimed to evaluate the chemical compositions and biological activities of quinoa, a novel and excellent food crop. Quinoa extract and its fractions were prepared by ethanol extraction and liquid-liquid extraction, including ethanol crude extract, and petroleum ether, chloroform, ethyl acetate (EAF), and n-butanol and water fractions. The total phenolic and flavonoid contents, antioxidant activities, α-glucosidase and acetylcholinesterase inhibitory abilities of the extract and fractions were further determined. Based on these foundations, the chemical composition of the EAF fraction exhibiting the strongest functional activity was analyzed by ultra-performance liquid chromatography-mass spectrometry. The results showed the EAF fraction had the highest phenolic and flavonoid contents, and the highest antioxidant activities, as well as the strongest α-glucosidase and acetylcholinesterase inhibitory abilities, which is even better than the positive control. The phytochemical composition of the EAF fraction indicated that 661 and 243 metabolites were identified in positive and negative ion modes, which were classified into superclass, class and subclass levels, respectively. Phenolic acids and flavonoids were the major bioactive compounds in the EAF fraction. This study found that quinoa, especially its ethyl acetate fraction, had the potential for the development of natural antioxidants, acetylcholinesterase inhibitors, and hypoglycemic agents.
14
Zimmerman, Sabrina A., Jean-Francois Tomb e James G. Ferry. "Characterization of CamH from Methanosarcina thermophila, Founding Member of a Subclass of the γ Class of Carbonic Anhydrases". Journal of Bacteriology 192, n. 5 (18 dicembre 2009): 1353–60. http://dx.doi.org/10.1128/jb.01164-09.
Abstract (sommario):
ABSTRACT The homotrimeric enzyme Mt-Cam from Methanosarcina thermophila is the archetype of the γ class of carbonic anhydrases. A search of databases queried with Mt-Cam revealed that a majority of the homologs comprise a putative subclass (CamH) in which there is major conservation of all of the residues essential for the archetype Mt-Cam except Glu62 and an acidic loop containing the essential proton shuttle residue Glu84. The CamH homolog from M. thermophila (Mt-CamH) was overproduced in Escherichia coli and characterized to validate its activity and initiate an investigation of the CamH subclass. The Mt-CamH homotrimer purified from E. coli cultured with supplemental zinc (Zn-Mt-CamH) contained 0.71 zinc and 0.15 iron per monomer and had k cat and kcat /Km values that were substantially lower than those for the zinc form of Mt-Cam (Zn-Mt-Cam). Mt-CamH purified from E. coli cultured with supplemental iron (Fe-Mt-CamH) was also a trimer containing 0.15 iron per monomer and only a trace amount of zinc and had an effective k cat (k cat eff) value normalized for iron that was 6-fold less than that for the iron form of Mt-Cam, whereas the k cat/Km eff was similar to that for Fe-Mt-Cam. Addition of 50 mM imidazole to the assay buffer increased the k cat eff of Fe-Mt-CamH more than 4-fold. Fe-Mt-CamH lost activity when it was exposed to air or 3% H2O2, which supports the hypothesis that Fe2+ has a role in the active site. The k cat for Fe-Mt-CamH was dependent on the concentration of buffer in a way that indicates that it acts as a second substrate in a “ping-pong” mechanism accepting a proton. The k cat/Km was not dependent on the buffer, consistent with the mechanism for all carbonic anhydrases in which the interconversion of CO2 and HCO3 − is separate from intermolecular proton transfer.
15
Finkenwirth, Friedrich, Franziska Kirsch e Thomas Eitinger. "Complex Stability During the Transport Cycle of a Subclass I ECF Transporter". Biochemistry 56, n. 34 (15 agosto 2017): 4578–83. http://dx.doi.org/10.1021/acs.biochem.7b00390.
16
Chew, C. S., K. Nakamura e A. C. Petropoulos. "Multiple actions of epidermal growth factor and TGF-alpha on rabbit gastric parietal cell function". American Journal of Physiology-Gastrointestinal and Liver Physiology 267, n. 5 (1 novembre 1994): G818—G826. http://dx.doi.org/10.1152/ajpgi.1994.267.5.g818.
Abstract (sommario):
Parietal cells in primary culture and freshly isolated parietal cells were used to compare acute and chronic effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on acid-secretory related activity, measured as accumulation of the weak base, [14C]aminopyrine (AP). EGF and TGF-alpha chronically enhanced basal and agonist-stimulated AP accumulation (mean effective concentration 0.6-0.8 nM) but acutely inhibited responses to histamine and carbachol (half-maximal inhibitory concentration approximately 4 nM). Pertussis toxin (250 ng/ml, 4 h) suppressed acute EGF inhibition of histamine-stimulated AP accumulation but not the chronic enhancement. A subclass of tyrosine kinase inhibitors suppressed chronic EGF effects (genistein > tyrphostin B56 >>> tyrphostin B42), whereas tyrphostin A25, lavendustin A, and the inactive genistein analogue, daidzein, had no significant effect. In contrast, histamine-stimulated AP accumulation was acutely potentiated by genistein, daidzein, and tyrphostin B42, but not tyrphostin B56. Reduced phosphorylation of a 44- to 45-kDa protein with an isoelectric point of approximately 7 [phosphoprotein (pp) 44] was correlated with chronic inhibition but not with acute potentiation by specific tyrosine kinase inhibitors. Preliminary data indicate that pp44 is a member of the mitogen-activated protein kinase family of tyrosine/threonine kinases (also known as extracellular signal-related kinases). We propose that 1) EGF and/or TGF-alpha modulates parietal cell function by multiple signaling pathways, 2) a soluble tyrosine kinase may be involved in the mediation of the chronic effects of EGF, and 3) acute potentiation of histamine-stimulated AP accumulation by certain tyrosine kinase inhibitors and daidzein is probably not mediated by receptor-associated tyrosine kinases.
17
Gadella, T. W., e T. M. Jovin. "Oligomerization of epidermal growth factor receptors on A431 cells studied by time-resolved fluorescence imaging microscopy. A stereochemical model for tyrosine kinase receptor activation." Journal of Cell Biology 129, n. 6 (15 giugno 1995): 1543–58. http://dx.doi.org/10.1083/jcb.129.6.1543.
Abstract (sommario):
The aggregation states of the epidermal growth factor receptor (EGFR) on single A431 human epidermoid carcinoma cells were assessed with two new techniques for determining fluorescence resonance energy transfer: donor photobleaching fluorescence resonance energy transfer (pbFRET) microscopy and fluorescence lifetime imaging microscopy (FLIM). Fluorescein-(donor) and rhodamine-(acceptor) labeled EGF were bound to the cells and the extent of oligomerization was monitored by the spatially resolved FRET efficiency as a function of the donor/acceptor ratio and treatment conditions. An average FRET efficiency of 5% was determined after a low temperature (4 degrees C) incubation with the fluorescent EGF analogs for 40 min. A subsequent elevation of the temperature for 5 min caused a substantial increase of the average FRET efficiency to 14% at 20 degrees C and 31% at 37 degrees C. In the context of a two-state (monomer/dimer) model for the EGFR, these FRET efficiencies were consistent with minimal average receptor dimerizations of 13, 36, and 69% at 4, 20, and 37 degrees C, respectively. A431 cells were pretreated with the monoclonal antibody mAb 2E9 that specifically blocks EGF binding to the predominant population of low affinity EGFR (15). The average FRET efficiency increased dramatically to 28% at 4 degrees C, indicative of a minimal receptor dimerization of 65% for the subpopulation of high affinity receptors. These results are in accordance with prior studies indicating that binding of EGF leads to a fast and temperature-dependent microclustering of EGFR, but suggest in addition that the high affinity functional subclass of receptors on quiescent A431 cells are present in a predimerized or oligomerized state. We propose that the transmission of the external ligand-binding signal to the cytoplasmic domain is effected by a concerted relative rotational rearrangement of the monomeric units comprising the dimeric receptor, thereby potentiating a mutual activation of the tyrosine kinase domains.
18
Mabel Cruz, Rodríguez, Báez Gretchen Bergado, Luna Yerandy Hechevarría, Fernández Diana Rosa Hernández, Palomo Addys González, Suárez Narjara González, Castillo Carlos Yordan González, Lorenzo María del Carmen Luzardo, García Lisset Chao e Ramírez Belinda Sánchez. "The combination of very-small size proteoliposomes and alum is a safe adjuvant alternative for inducing anti-EGF antibodies: a preclinical study". Archives of Cancer Science and Therapy 6, n. 1 (20 settembre 2022): 018–30. http://dx.doi.org/10.29328/journal.acst.1001029.
Abstract (sommario):
Immunization with human recombinant EGF chemically bound to the P64k protein of Neisseria meningitides (hrEGF-P64k) and adjuvanted in Montanide ISA 51 VG (Montanide) is an efficient strategy to induce polyclonal antibodies (PAbs) response targeting this self -antigen in cancer patients, which is the basis of the CIMAvax-EGF vaccine. The neutralizing potential of EGF-specific induced PAbs supports promising clinical data obtained to date with this vaccine. Herein, we evaluated a combination of very small-size proteoliposomes (VSSP) and aluminum hydroxide (Alum) as a novel adjuvant to induce specific PAbs with neutralizing and anti-proliferative properties on tumor cells, considering EGF as a model antigen. Toxicity at the injection site was not detected for the vaccine formulation containing VSSP/Alum, and it was immunogenic in BALB/c mice, as evidenced by the induction of high titers of EGF-specific polyclonal antibodies (PAbs). While schedule optimization increased the magnitude of the PAbs response induced by VSSP/Alum, induced PAbs’s avidity and intrinsic neutralizing potential were comparable to the humoral response induced by Montanide. Also, VSSP addition switched IgG subclasses distribution into a Th1-like pattern, as obtained with Montanide and desirable for a cancer vaccine. Finally, equivalent PAbs titers were induced by the vaccine formulations adjuvanted in VSSP/Alum or Montanide in tumor-bearing-mice, and immunosuppressed mice, suggesting the feasibility of the VSSP/Alum combined adjuvant for inducing anti-EGF antibodies in cancer patients at advanced stages of the disease.
19
Sinha, Abhilasha, Yong Zou, Ayushi S. Patel, Seungyeul Yoo, Feng Jiang, Takashi Sato, Ranran Kong et al. "Early-Stage Lung Adenocarcinoma MDM2 Genomic Amplification Predicts Clinical Outcome and Response to Targeted Therapy". Cancers 14, n. 3 (29 gennaio 2022): 708. http://dx.doi.org/10.3390/cancers14030708.
Abstract (sommario):
Lung cancer is the most common cause of cancer-related deaths in both men and women, accounting for one-quarter of total cancer-related mortality globally. Lung adenocarcinoma is the major subtype of non-small cell lung cancer (NSCLC) and accounts for around 40% of lung cancer cases. Lung adenocarcinoma is a highly heterogeneous disease and patients often display variable histopathological morphology, genetic alterations, and genomic aberrations. Recent advances in transcriptomic and genetic profiling of lung adenocarcinoma by investigators, including our group, has provided better stratification of this heterogeneous disease, which can facilitate devising better treatment strategies suitable for targeted patient cohorts. In a recent study we have shown gene expression profiling identified novel clustering of early stage LUAD patients and correlated with tumor invasiveness and patient survival. In this study, we focused on copy number alterations in LUAD patients. SNP array data identified amplification at chromosome 12q15 on MDM2 locus and protein overexpression in a subclass of LUAD patients with an invasive subtype of the disease. High copy number amplification and protein expression in this subclass correlated with poor overall survival. We hypothesized that MDM2 copy number and overexpression predict response to MDM2-targeted therapy. In vitro functional data on a panel of LUAD cells showed that MDM2-targeted therapy effectively suppresses cell proliferation, migration, and invasion in cells with MDM2 amplification/overexpression but not in cells without MDM2 amplification, independent of p53 status. To determine the key signaling mechanisms, we used RNA sequencing (RNA seq) to examine the response to therapy in MDM2-amplified/overexpressing p53 mutant and wild-type LUAD cells. RNA seq data shows that in MDM2-amplified/overexpression with p53 wild-type condition, the E2F → PEG10 → MMPs pathway is operative, while in p53 mutant genetic background, MDM2-targeted therapy abrogates tumor progression in LUAD cells by suppressing epithelial to mesenchymal transition (EMT) signaling. Our study provides a potentially clinically relevant strategy of selecting LUAD patients for MDM2-targeted therapy that may provide for increased response rates and, thus, better survival.
20
Ikeuchi, Momoko, Akira Iwase, Tasuku Ito, Hayato Tanaka, David S. Favero, Ayako Kawamura, Shingo Sakamoto et al. "Wound-inducible WUSCHEL-RELATED HOMEOBOX 13 is required for callus growth and organ reconnection". Plant Physiology 188, n. 1 (3 novembre 2021): 425–41. http://dx.doi.org/10.1093/plphys/kiab510.
Abstract (sommario):
Abstract Highly efficient tissue repair is pivotal for surviving damage-associated stress. Plants generate callus upon injury to heal wound sites, yet regulatory mechanisms of tissue repair remain elusive. Here, we identified WUSCHEL-RELATED HOMEOBOX 13 (WOX13) as a key regulator of callus formation and organ adhesion in Arabidopsis (Arabidopsis thaliana). WOX13 belongs to an ancient subclade of the WOX family, and a previous study shows that WOX13 orthologs in the moss Physcomitrium patens (PpWOX13L) are involved in cellular reprogramming at wound sites. We found that the Arabidopsis wox13 mutant is totally defective in establishing organ reconnection upon grafting, suggesting that WOX13 is crucial for tissue repair in seed plants. WOX13 expression rapidly induced upon wounding, which was partly dependent on the activity of an AP2/ERF transcription factor, WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1). WOX13 in turn directly upregulated WIND2 and WIND3 to further promote cellular reprogramming and organ regeneration. We also found that WOX13 orchestrates the transcriptional induction of cell wall-modifying enzyme genes, such as GLYCOSYL HYDROLASE 9Bs, PECTATE LYASE LIKEs and EXPANSINs. Furthermore, the chemical composition of cell wall monosaccharides was markedly different in the wox13 mutant. These data together suggest that WOX13 modifies cell wall properties, which may facilitate efficient callus formation and organ reconnection. Furthermore, we found that PpWOX13L complements the Arabidopsis wox13 mutant, suggesting that the molecular function of WOX13 is partly conserved between mosses and seed plants. This study provides key insights into the conservation and functional diversification of the WOX gene family during land plant evolution.
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Zhang, Yuanyuan, Jeffrey Chu, Stephen Chan e Brandon Chan. "The generalised hyperbolic distribution and its subclass in the analysis of a new era of cryptocurrencies: Ethereum and its financial risk". Physica A: Statistical Mechanics and its Applications 526 (luglio 2019): 120900. http://dx.doi.org/10.1016/j.physa.2019.04.136.
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Vishnu, A., J. Choo, K. H. Masaki, R. H. Mackey, E. Barinas-Mitchell, C. Shin, B. J. Willcox et al. "Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study". Journal of Human Hypertension 28, n. 2 (4 luglio 2013): 111–17. http://dx.doi.org/10.1038/jhh.2013.60.
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Wurster, A. L., G. Siu, J. M. Leiden e S. M. Hedrick. "Elf-1 binds to a critical element in a second CD4 enhancer". Molecular and Cellular Biology 14, n. 10 (ottobre 1994): 6452–63. http://dx.doi.org/10.1128/mcb.14.10.6452-6463.1994.
Abstract (sommario):
The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells). We have studied the regulation CD4 gene transcription during T-cell development in an attempt to gain an understanding of the molecular mechanisms involved in T-cell development and differentiation. Here we present the identification of a second transcriptional enhancer in the murine CD4 locus 24 kb upstream of the CD4 promoter. This enhancer is active in mature T cells and is especially active in CD4+ helper T cells. A number of nuclear proteins bind to elements in the minimal CD4 enhancer that includes consensus sites for AP-1, Sp1, Gata, and Ets transcription factor families. We find that the Ets consensus site is crucial for enhancer activity and that the recently identified Ets factor, Elf-1, which is expressed at high levels in T cells and involved in the regulation of several other T-cell-specific genes, is a dominant protein in T-cell nuclear extracts that binds to this site.
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Wurster, A. L., G. Siu, J. M. Leiden e S. M. Hedrick. "Elf-1 binds to a critical element in a second CD4 enhancer." Molecular and Cellular Biology 14, n. 10 (ottobre 1994): 6452–63. http://dx.doi.org/10.1128/mcb.14.10.6452.
Abstract (sommario):
The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells). We have studied the regulation CD4 gene transcription during T-cell development in an attempt to gain an understanding of the molecular mechanisms involved in T-cell development and differentiation. Here we present the identification of a second transcriptional enhancer in the murine CD4 locus 24 kb upstream of the CD4 promoter. This enhancer is active in mature T cells and is especially active in CD4+ helper T cells. A number of nuclear proteins bind to elements in the minimal CD4 enhancer that includes consensus sites for AP-1, Sp1, Gata, and Ets transcription factor families. We find that the Ets consensus site is crucial for enhancer activity and that the recently identified Ets factor, Elf-1, which is expressed at high levels in T cells and involved in the regulation of several other T-cell-specific genes, is a dominant protein in T-cell nuclear extracts that binds to this site.
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Choo, Jina, Hirotsugu Ueshima, J. David Curb, Chol Shin, Rhobert W. Evans, Aiman El-Saed, Takashi Kadowaki et al. "Serum n−6 fatty acids and lipoprotein subclasses in middle-aged men: the population-based cross-sectional ERA-JUMP Study". American Journal of Clinical Nutrition 91, n. 5 (31 marzo 2010): 1195–203. http://dx.doi.org/10.3945/ajcn.2009.28500.
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Nagatomo, Yuji, Daniel Li, Jennifer Kirsop, Alan Borowski, Akanksha Thakur e W. H. Wilson Tang. "Autoantibodies Specifically Against β1 Adrenergic Receptors and Adverse Clinical Outcome in Patients With Chronic Systolic Heart Failure in the β-Blocker Era: The Importance of Immunoglobulin G3 Subclass". Journal of Cardiac Failure 22, n. 6 (giugno 2016): 417–22. http://dx.doi.org/10.1016/j.cardfail.2016.03.005.
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Halimeh, Susan, Stephan Dreher, Thorsten Rosenbaum, Martin Rekus, Hannelore Rott, Ulrike Nowak-Gottl e Britta Faeser. "Infantile SVT in Consequence of a Congenital Antithrombin Deficiency". Blood 118, n. 21 (18 novembre 2011): 5260. http://dx.doi.org/10.1182/blood.v118.21.5260.5260.
Abstract (sommario):
Abstract Abstract 5260 The liver-made antithrombin is a natural coagulation inhibitor in human blood. Exceptionally it takes effect in inhibiting the coagulation-supporting factors IIa (thrombin) and Xa. A congenital antithrombin deficiency leads to thrombosis and has to be heterozygous, because homozygous ATIII deficiencies are incompatible with life. Unfortunately it's dominant inherited. In 1965 a congenital ATIII deficiency was first detected as a hereditary disease. There are two different types, type I describes a less produced ATIII deficiency, type II is a function loss of ATIII. Special testing can define more subclasses. In cases of congenital ATIII deficiency, vascular blockage (thrombosis) appears, especially in leg veins. Released clots can cause pulmonal embolism, rarely are other arteries affected. Although this disease is hereditary, it appears mostly between ages of 15 'til 30. Clinical trials showed that 80% of affected patient have a thrombosis or embolism until the age of 40. Has there be no kind of illness appeared until there, it's very improbable to get one becaus eof ATIII deficiency. Every hundredth below the age of 70, who comes to a health care center has a ATIII deficiency. In total population it's a freqzuency of 1:2000 until 1:5000. Mostly there's a deficiency nown in familary history why they are investigated. The residual activity is between 40 – 60%. Conclusion: Most cases of thrombosis are treated with heparine. Heparin binds to ATIII, so ATIII can be much more effective and inhibits thrombin and Xa much more intense. For the future we have to make sure that antithrombin deficiencies especially in childhood have to be treated with phenprocumone. Disclosures: No relevant conflicts of interest to declare.
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Goswami, Partha Pratim, e Aruna Goswami. "Spectroscopic Study of Ba and CEMP-s Stars: Mass Distribution of AGB Progenitors* †". Astronomical Journal 165, n. 4 (10 marzo 2023): 154. http://dx.doi.org/10.3847/1538-3881/aca971.
Abstract (sommario):
Abstract We have performed detailed high-resolution spectroscopic analysis on seven metal-poor stars (BD+75 348, BD+09 3019, HD238020, HE0319–0215, HE0507–1653, HE0930–0018, HE1023–1504) and derived their atmospheric parameters T eff, log g, [Fe/H], and microturbulent velocity (ξ). The metallicity range is found to be –2.57 < [Fe/H] < –0.42. The elemental abundances of 17 light elements and 12 heavy elements are estimated. We have classified BD+75 348 and BD+09 3019 as strong Ba stars, HD238020 as a mild Ba star, and the remaining four objects as CEMP-s stars. We have estimated the masses of the stars from Hertzsprung–Russel (HR) diagram, and, compiling the data of 205 Ba stars from literature, estimated the mass distribution of Ba stars. We have also estimated the initial masses of the companion AGBs of the program stars as well as the masses of the companion AGBs of 159 Ba and 36 CEMP-s stars from literature, with the help of a parametric-model-based analysis using FRUITY models. While the primary mass distribution of mild Ba stars peaks at 3.7 M ⊙, for the strong Ba stars the peak appears at 2.5 M ⊙. We, therefore, propose that the initial masses of the progenitor AGBs dominantly control the formation of mild and strong Ba stars. However, a clear overlap, in the range 1.3–4.0 M ⊙, noticed between the progenitor masses of both the subclasses of Ba stars, may indicate that other factors, such as the metallicities and the orbital periods, may also have significant contributions. The progenitor AGBs’ mass distribution of CEMP-s stars is found to peak at 2.03 M ⊙.
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Ta, Hoang Dang Khoa, Do Thi Minh Xuan, Wan-Chun Tang, Gangga Anuraga, Yi-Chun Ni, Syu-Ruei Pan, Yung-Fu Wu et al. "Novel Insights into the Prognosis and Immunological Value of the SLC35A (Solute Carrier 35A) Family Genes in Human Breast Cancer". Biomedicines 9, n. 12 (30 novembre 2021): 1804. http://dx.doi.org/10.3390/biomedicines9121804.
Abstract (sommario):
According to statistics 2020, female breast cancer (BRCA) became the most commonly diagnosed malignancy worldwide. Prognosis of BRCA patients is still poor, especially in population with advanced or metastatic. Particular functions of each members of the solute carrier 35A (SLC35A) gene family in human BRCA are still unknown regardless of awareness that they play critical roles in tumorigenesis and progression. Using integrated bioinformatics analyses to identify therapeutic targets for specific cancers based on transcriptomics, proteomics, and high-throughput sequencing, we obtained new information and a better understanding of potential underlying molecular mechanisms. Leveraging BRCA dataset that belongs to The Cancer Genome Atlas (TCGA), which were employed to clarify SLC35A gene expression levels. Then we used a bioinformatics approach to investigate biological processes connected to SLC35A family genes in BRCA development. Beside that, the Kaplan–Meier estimator was leveraged to explore predictive values of SLC35A family genes in BCRA patients. Among individuals of this family gene, expression levels of SLC35A2 were substantially related to poor prognostic values, result from a hazard ratio of 1.3 (with 95 percent confidence interval (95% CI: 1.18–1.44), the p for trend (ptrend) is 3.1 × 10−7). Furthermore, a functional enrichment analysis showed that SLC35A2 was correlated with hypoxia-inducible factor 1A (HIF1A), heat shock protein (HSP), E2 transcription factor (E2F), DNA damage, and cell cycle-related signaling. Infiltration levels observed in specific types of immune cell, especially the cluster of differentiation found on macrophages and neutrophils, were positively linked with SLC35A2 expression in multiple BRCA subclasses (luminal A, luminal B, basal, and human epidermal growth factor receptor 2). Collectively, SLC35A2 expression was associated with a lower recurrence-free survival rate, suggesting that it could be used as a biomarker in treating BRCA.
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Tschida, Barbara, Dylan Duerre, Mandy Taisto e Adrienne Watson. "TMOD-20. A SWINE MODEL OF GLIOBLASTOMA INDUCED BY SOMATIC GENE MODIFICATION". Neuro-Oncology 22, Supplement_2 (novembre 2020): ii232. http://dx.doi.org/10.1093/neuonc/noaa215.971.
Abstract (sommario):
Abstract Glioblastoma (GBM) is the most common and malignant primary brain tumor. Novel therapeutic development for GBM is needed since the standard of care universally fails to cure patients and the five-year survival rate remains below 10%. GBM therapeutic development is hampered by the lack of relevant large animal models for preclinical studies. To mitigate this problem, we are developing a model of GBM in outbred, immune-proficient swine which have comparable brain size and anatomy to humans. We developed methods for introducing genome engineering tools to minipig brain cells in vivo by direct injection of gene delivery reagents to the lateral ventricle. Using this technique, we have delivered a combination of expression vectors for oncogenes and targeted nucleases to disrupt tumor suppressor genes commonly altered in human GBM to alter six major human GBM-associated signaling pathways in a cohort of minipigs (Ras, Pi3k, p53, Rb/E2F, Pdgf, and the alternative lengthening of telomeres (ALT) pathways). These minipigs are being monitored for tumorigenesis using a secreted reporter, detectable through a simple luminescence-based blood test. Resulting tumors will be examined molecularly to detect the pathway-associated alterations in tumor tissue and determine the resemblance to human GBM. We hypothesize that this somatic cell gene-modification platform we have developed in the minipig will facilitate the efficient production of brain tumors that histologically and genetically resemble human GBM. It will allow the production of tumors that are genetically heterogeneous, of specified molecular subclasses, containing therapeutic targets of interest, and in the context of genetic backgrounds of interest. This minipig model of GBM will be applied towards preclinical therapeutic studies, imaging studies using human clinical grade equipment, and surgical technique development, to improve clinical trial success rates and patient outcomes. Funding for this study is provided by the National Institutes of Health through SBIR grant # 1R43CA235837-01A1.
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Federici, Elisa, Gianluca Civenni, Aleksandra Kokanovic, Giada Sandrini, Luca Guarrera, Simone Mosole, Alessia Cacciatore et al. "Abstract 5471: PRT2527, a novel highly selective cyclin-dependent kinase 9 (CDK9) inhibitor, is active in preclinical models of prostate cancer". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 5471. http://dx.doi.org/10.1158/1538-7445.am2022-5471.
Abstract (sommario):
Abstract CDK9 is a serine/threonine kinase belonging to the subclass of the transcription associated CDKs. CDK9 complexes with cyclin T and cyclin K, the positive transcription elongation factor b (P-TEFb), and phosphorylates Serine 2 of RNA polymerase II (pSer2 RNAPII) to activate transcription. Consequently, targeting CDK9 could effectively interfere with epigenetic and transcriptional reprogramming and prevent disease progression and treatment resistance in human cancers. Androgen receptor (AR)-dependence in prostate cancer is linked to CDK9 function. CDK9 stabilizes AR-associated proteins, and pharmacological inhibition of CDK9 can inhibit AR, AR variants, and their downstream transcription programs. We evaluated the novel CDK9 inhibitor, PRT2527, in prostate cancer models to evaluate its effects on cell proliferation, stem-like tumor cells, and tumor growth. PRT2527 is a potent inhibitor of CDK9/CyclinT1 complex, and when evaluated at concentration 200 times the biochemical IC50, PRT2527 was highly selective for CDK9 inhibition. We verified in biochemical assays the ability of PRT2527 to suppress pSer2 RNAPII and reduce expression of c-Myc, a common target of CDK9, in a concentration-dependent manner in multiple human prostate cancer cell lines. PRT2527 also inhibited c-Myc-dependent transcription in vitro in luciferase reporter assays. Furthermore, RNA sequencing showed altered expression of several genes with significant enrichment of c-Myc and E2F targets and RNAPII dependent transcription among downregulated genes in PRT2527-treated VCaP cells. In vitro, PRT2527 inhibited the proliferation of androgen-dependent and androgen-independent prostate cancer cell lines (IC50, ≤50 nM). PRT2527 was highly effective (IC50, ≤10 nM) in tumor-spheroid assays in blocking the growth of stem-like tumor cells and significantly suppressed the in vitro growth of tumor organoids from both human cell lines and patient-derived xenografts (PDXs). In mice, PRT2527 IV administration reduced pSer2 RNAPII in tumor xenografts and c-Myc-dependent transcriptional activity in a DU145 luminescence reporter model. PRT2527 administration in mice significantly reduced growth of PDX LuCaP 35 (castration-sensitive, adenocarcinoma) and LuCaP 145.2 (castration-resistant, neuroendocrine) along with the fraction of tumor-initiating stem-like cells in ex vivo assays. PRT2527 reduced pSer2 RNAPII in both PDXs, whereas c-Myc decreased in LuCaP 35 and Sox2 in LuCaP 145.2, relative to basal expression levels. Collectively, our data demonstrate that PRT2527 has potent pharmacodynamic and antitumor activity in multiple models of castration-sensitive and castration-resistant prostate cancer. PRT2527 is advancing into phase 1 studies in solid tumors. Citation Format: Elisa Federici, Gianluca Civenni, Aleksandra Kokanovic, Giada Sandrini, Luca Guarrera, Simone Mosole, Alessia Cacciatore, Valeria Uboldi, Manuel Lessi, Giovanni Papa, Domenico Albino, Elisa Storelli, Jessica Merulla, Andrea Rinaldi, Marco Bolis, Yang Zhang, Kris Vaddi, Peggy Scherle, Bruce Ruggeri, Giuseppina M. Carbone, Carlo V. Catapano. PRT2527, a novel highly selective cyclin-dependent kinase 9 (CDK9) inhibitor, is active in preclinical models of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5471.
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Sekikawa, Akira, Hirotsugu Ueshima, Kim Sutton-Tyrrell, Takashi Kadowaki, Aiman El-Saed, Tomonori Okamura, Tomoko Takamiya et al. "Intima-media thickness of the carotid artery and the distribution of lipoprotein subclasses in men aged 40 to 49 years between whites in the United States and the Japanese in Japan for the ERA JUMP study". Metabolism 57, n. 2 (febbraio 2008): 177–82. http://dx.doi.org/10.1016/j.metabol.2007.08.022.
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Farrar, Jason, Michael Ochs, David W. Lee, C. C. Talbot, Jonathan Buckley, Soheil Meshinchi e Robert J. Arceci. "Coordinate Changes In RNA Expression, Transcript Splicing, and DNA Methylation In Pediatric AML". Blood 122, n. 21 (15 novembre 2013): 3761. http://dx.doi.org/10.1182/blood.v122.21.3761.3761.
Abstract (sommario):
Abstract While mutations of splicing and epigenetic factors have been reported in adult AML and related myeloid disorders, relatively few such changes have been identified in pediatric AML. We previously identified a chromatin remodeling helicase, PASG (SMARCA6, HELLS, LSH), by down-regulation in AML cell lines following cytokine withdrawal and identified an alternatively spliced variant lacking a highly conserved (STRAGGLG) domain. To assess the prevalence of this splicing variant (PASGΔ75) in pediatric AML, we tested 167 diagnostic specimens from the TARGET-AML cohort for fractional PASGΔ75 expression (PASGΔ75/PASG) using a discriminatory RT-qPCR assay. These studies demonstrated a broad, continuous distribution of PASGΔ75 with right skew (mean PASGΔ75: 26%, interquartile range: 9% – 41%) that was not significantly associated with cytogenetic class (inv16, t(8;21), MLL, normal) or FAB subtype. For further comparison, specimens were quantized by PASGΔ75 quartile. Given reported associations between loss of PASG function and abnormalities of genomic methylation, we tested 48 AML specimens at the extremes of the PASGΔ75 distribution for total 5-methylcytosine (5-mC) content by liquid chromatography/tandem mass spectrometry. The mean total methylation was significantly lower in the high compared to the low PASGΔ75 groups (mean 5-mC 3.95% vs. 4.22% of cytosine, p=0.015 Mann-Whitney). To identify specific regions of altered methylation, we used high-throughput sequencing of DNA enriched by pull-down with the methyl binding domain fragment of MBD2 (MBD-Seq). Comparison of summed methylation signal across regions flanking RefSeq transcriptional start sites (TSS) showed the expected decrease in methylation just upstream of the TSS in both groups. However, methylation more distal to the TSS was proportionally lower in PASGΔ75 high than PASGΔ75 low samples (Fig 1a). To evaluate methylation at CpG islands (CGI), UCSC CGI were scaled to 500 bp and MBD-Seq data were summed across 20Kb flanking CGI. While both groups showed the anticipated increase in methylation signal on CGI, methylation in the shore regions immediately flanking CGI was proportionally lower in high PASGΔ75 compared to low PASGΔ75 samples (Fig 1b), further suggesting epigenetic differences between these sample groups. Because we were unable to identify sequence variants in PASG intron 18 or flanking exons that might explain alternative splicing, we asked whether expression of PASGΔ75 was associated with global changes in transcript splicing. We evaluated gene expression patterns on the Affymetrix HuGene array, with assessment of alternative splicing using Partek software alternative splicing (altsplice) algorithm for quartile-grouped samples. In contrast to comparison of adjacent quartile groups, which showed modest changes in expression and relatively few transcripts with significant altsplice scores, comparison of the highest and lowest quartile samples showed marked changes in gene expression and a large number of alternatively spiced transcripts as assessed by significance of the altsplice score (Fig 2). In addition to splicing changes, these analyses suggested marked differences in gene expression patterns of AML specimens grouped by PASGΔ75 quartile, with clear separation of Q1 and Q4 samples by principal components analysis. Using a conservative Wilcoxon gene sets test and limiting ourselves to small, curated Biocarta pathways, we found expression patterns associated with high deletion variant expression strongly linked to overlapping pathways involving DNA repair, replication, and cell cycle progression. Table Pathways (Biocarta) Pathway Class Benjamini Hochberg Corrected p-Value ATR/BRCA1/BRCA2 DNA Damage Response 1.3E-6 RB/DNA Damage DNA Damage Response 3.5E-3 p27 Phosphorylation Cell Cycle Progression 3.5E-3 G2/M Checkpoint Cell Cycle Progression 3.5E-3 G1/S Checkpoint Cell Cycle Progression 4.1E-3 PLK3 Cell Cycle Progression 4.1E-3 MEF2D Apoptosis 0.01 SRC/PTPa Cell Cycle Progression 0.02 Mitochondrial Acetyl-Co Shuttle Metabolism 0.02 p53 Signaling DNA Damage Response 0.04 E2F-1 Cell Cycle Progression 0.04 ATM Signaling DNA Damage Response 0.04 These data suggest the existence of a previously unrecognized AML subclass characterized by widespread and coordinated changes in RNA expression, alternative transcript splicing, and epigenetic modifications. Disclosures: No relevant conflicts of interest to declare.
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Meng, Sida, Xinyu Yan, Yinglan Piao, Shizhen Li, Xin Wang, Jing Jiang, Yue Liang e Wenxing Pang. "Multiple transcription factors involved in the response of Chinese cabbage against Plasmodiophora brassicae". Frontiers in Plant Science 15 (6 giugno 2024). http://dx.doi.org/10.3389/fpls.2024.1391173.
Abstract (sommario):
Clubroot disease, which is caused by the obligate biotrophic protist Plasmodiophora brassicae, leads to the formation of galls, commonly known as pathogen-induced tumors, on the roots of infected plants. The identification of crucial regulators of host tumor formation is essential to unravel the mechanisms underlying the proliferation and differentiation of P. brassicae within plant cells. To gain insight into this process, transcriptomic analysis was conducted to identify key genes associated with both primary and secondary infection of P. brassicae in Chinese cabbage. Our results demonstrate that the k-means clustering of subclass 1, which exhibited specific trends, was closely linked to the infection process of P. brassicae. Of the 1610 differentially expressed genes (DEGs) annotated in subclass 1, 782 were identified as transcription factors belonging to 49 transcription factor families, including bHLH, B3, NAC, MYB_related, WRKY, bZIP, C2H2, and ERF. In the primary infection, several genes, including the predicted Brassica rapa probable pectate lyase, RPM1-interacting protein 4-like, L-type lectin-domain-containing receptor kinase, G-type lectin S-receptor-like serine, B. rapa photosystem II 22 kDa protein, and MLP-like protein, showed significant upregulation. In the secondary infection stage, 45 of 50 overlapping DEGs were upregulated. These upregulated DEGs included the predicted B. rapa endoglucanase, long-chain acyl-CoA synthetase, WRKY transcription factor, NAC domain-containing protein, cell division control protein, auxin-induced protein, and protein variation in compound-triggered root growth response-like and xyloglucan glycosyltransferases. In both the primary and secondary infection stages, the DEGs were predicted to be Brassica rapa putative disease resistance proteins, L-type lectin domain-containing receptor kinases, ferredoxin-NADP reductases, 1-aminocyclopropane-1-carboxylate synthases, histone deacetylases, UDP-glycosyltransferases, putative glycerol-3-phosphate transporters, and chlorophyll a-binding proteins, which are closely associated with plant defense responses, biosynthetic processes, carbohydrate transport, and photosynthesis. This study revealed the pivotal role of transcription factors in the initiation of infection and establishment of intracellular parasitic relationships during the primary infection stage, as well as the proliferation and differentiation of the pathogen within the host cell during the secondary infection stage.
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Reboledo, Guillermo, Astrid Agorio, Lucía Vignale, Alfonso Alvarez e Inés Ponce De León. "The moss-specific transcription factor PpERF24 positively modulates immunity against fungal pathogens in Physcomitrium patens". Frontiers in Plant Science 13 (15 settembre 2022). http://dx.doi.org/10.3389/fpls.2022.908682.
Abstract (sommario):
APETALA2/ethylene response factors (AP2/ERFs) transcription factors (TFs) have greatly expanded in land plants compared to algae. In angiosperms, AP2/ERFs play important regulatory functions in plant defenses against pathogens and abiotic stress by controlling the expression of target genes. In the moss Physcomitrium patens, a high number of members of the ERF family are induced during pathogen infection, suggesting that they are important regulators in bryophyte immunity. In the current study, we analyzed a P. patens pathogen-inducible ERF family member designated as PpERF24. Orthologs of PpERF24 were only found in other mosses, while they were absent in the bryophytes Marchantia polymorpha and Anthoceros agrestis, the vascular plant Selaginella moellendorffii, and angiosperms. We show that PpERF24 belongs to a moss-specific clade with distinctive amino acids features in the AP2 domain that binds to the DNA. Interestingly, all P. patens members of the PpERF24 subclade are induced by fungal pathogens. The function of PpERF24 during plant immunity was assessed by an overexpression approach and transcriptomic analysis. Overexpressing lines showed increased defenses to infection by the fungal pathogens Botrytis cinerea and Colletotrichum gloeosporioides evidenced by reduced cellular damage and fungal biomass compared to wild-type plants. Transcriptomic and RT-qPCR analysis revealed that PpERF24 positively regulates the expression levels of defense genes involved in transcriptional regulation, phenylpropanoid and jasmonate pathways, oxidative burst and pathogenesis-related (PR) genes. These findings give novel insights into potential mechanism by which PpERF24 increases plant defenses against several pathogens by regulating important players in plant immunity.
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Cao, Yang, Kexin Wang, Fengzhong Lu, Qi Li, Qingqing Yang, Bingliang Liu, Hayderbinkhalid Muhammad et al. "Comprehensive identification of maize ZmE2F transcription factors and the positive role of ZmE2F6 in response to drought stress". BMC Genomics 25, n. 1 (13 maggio 2024). http://dx.doi.org/10.1186/s12864-024-10369-0.
Abstract (sommario):
Abstract Background The early 2 factor (E2F) family is characterized as a kind of transcription factor that plays an important role in cell division, DNA damage repair, and cell size regulation. However, its stress response has not been well revealed. Results In this study, ZmE2F members were comprehensively identified in the maize genome, and 21 ZmE2F genes were identified, including eight E2F subclade members, seven DEL subfamily genes, and six DP genes. All ZmE2F proteins possessed the DNA-binding domain (DBD) characterized by conserved motif 1 with the RRIYD sequence. The ZmE2F genes were unevenly distributed on eight maize chromosomes, showed diversity in gene structure, expanded by gene duplication, and contained abundant stress-responsive elements in their promoter regions. Subsequently, the ZmE2F6 gene was cloned and functionally verified in drought response. The results showed that the ZmE2F6 protein interacted with ZmPP2C26, localized in the nucleus, and responded to drought treatment. The overexpression of ZmE2F6 enhanced drought tolerance in transgenic Arabidopsis with longer root length, higher survival rate, and biomass by upregulating stress-related gene transcription. Conclusions This study provides novel insights into a greater understanding and functional study of the E2F family in the stress response.
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Nakata, Miyuki T., Shingo Sakamoto, Nuoendagula, Shinya Kajita e Nobutaka Mitsuda. "Fiber Cell-Specific Expression of the VP16-Fused Ethylene Response Factor 41 Protein Increases Biomass Yield and Alters Lignin Composition". Frontiers in Plant Science 12 (30 aprile 2021). http://dx.doi.org/10.3389/fpls.2021.654655.
Abstract (sommario):
Arabidopsis thaliana transcription factors belonging to the ERFIIId and ERFIIIe subclade (ERFIIId/e) of the APETALA 2/ethylene response factor (AP2/ERF) family enhance primary cell wall (PCW) formation. These transcription factors activate expression of genes encoding PCW-type cellulose synthase (CESA) subunits and other genes for PCW biosynthesis. In this study, we show that fiber-specific expression of ERF035-VP16 and ERF041-VP16, which are VP16-fused proteins of ERFIIId/e members, promote cell wall thickening in a wild-type background with a concomitant increase of alcohol insoluble residues (cell wall content) per fresh weight (FW) and monosaccharides related to the PCW without affecting plant growth. Furthermore, in the ERF041-VP16 lines, the total amount of lignin and the syringyl (S)/guaiacyl (G) ratio decreased, and the enzymatic saccharification yield of glucose from cellulose per fresh weight improved. In these lines, PCW-type CESA genes were upregulated and ferulate 5-hydropxylase1 (F5H1), which is necessary for production of the S unit lignin, was downregulated. In addition, various changes in the expression levels of transcription factors regulating secondary cell wall (SCW) formation were observed. In conclusion, fiber cell-specific ERF041-VP16 improves biomass yield, increases PCW components, and alters lignin composition and deposition and may be suitable for use in future molecular breeding programs of biomass crops.
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PENTU, NARENDRA, SAI BINDU M e RAMA RAO T. "FLAVANOIDS: AN ERA OF NUTRACEUTICALS TURNING IN TO MEDICINAL AGENTS". Asian Journal of Pharmaceutical and Clinical Research, 7 giugno 2024, 9–17. http://dx.doi.org/10.22159/ajpcr.2024.v17i6.50514.
Abstract (sommario):
Flavonoids, present in plants, constitute a varied group of naturally occurring compounds well-known for their potential positive effects on health. These molecules present in fruits, vegetables, and beverages such as tea exhibit antioxidant, anti-inflammatory, and other bioactive properties that contribute to their positive impact on human health. In addition, flavonoids act as antioxidants, helping plants combat oxidative stress. Some flavonoids also participate in ultraviolet protection, defense against pathogens, and modulation of plant-microbe interactions. Flavonoids have a different subclass of flavones, flavonols, flavanones, flavan-3-ols, anthocyanins, and isoflavones. The term “bioavailability” describes how well the body absorbs and uses flavonoids, a broad class of plant-based chemicals. The chemical structure of flavonoids, the matrix of foods they are eaten interactions with other dietary components influence their bioavailability. This metabolism can lead to the formation of various metabolites, impacting the compounds’ bioactivity. Understanding these aspects is crucial for unlocking the full potential of flavonoids in promoting health and preventing diseases. Patents on flavonoids serve as legal protections for innovations related to these plant compounds. Companies and researchers seek patents to safeguard novel methods of extraction, synthesis, and applications ensuring exclusivity for a specified period. This exclusivity incentivizes investment in research and development, promoting the exploration of flavonoids for pharmaceuticals, food additives, and cosmetics. Ultimately, these legal protections encourage advancements in understanding and harnessing the diverse benefits of flavonoids across various industries.
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Dolfini, Diletta, Valentina Andrioletti e Roberto Mantovani. "Overexpression and alternative splicing of NF-YA in breast cancer". Scientific Reports 9, n. 1 (10 settembre 2019). http://dx.doi.org/10.1038/s41598-019-49297-5.
Abstract (sommario):
Abstract NF-Y is a CCAAT-binding trimeric transcription factor, whose regulome, interactome and oncogenic potential point to direct involvement in cellular transformation. Yet little is known about the levels of NF-Y subunits in tumors. We focused on breast carcinomas, and analyzed RNA-Seq datasets of TCGA and 54 BRCA cell lines at gene and isoforms level. We partitioned all tumors in the four major subclasses. NF-YA, but not histone-fold subunits NF-YB/NF-YC, is globally overexpressed, correlating with the proliferative Ki67 marker and a common set of 840 genes, with cell-cycle, metabolism GO terms. Their promoters are enriched in NF-Y, GC-rich and E2F sites. Surprisingly, there is an isoform switch, with the “short” isoform -NF-YAs- becoming predominant in tumors. E2F genes are also overexpressed in BRCA, but no switch in isoforms is observed. In Basal-like Claudinlow cell lines and tumors, expression of NF-YAl -long- isoform is high, together with 11 typical EMT markers and low levels of basal Keratins. Analysis of Progression-Free-Intervals indicates that tumors with unbalance of NF-YA isoforms ratios have worst clinical outcomes. The data suggest that NF-YA overexpression increases CCAAT-dependent, pro-growth genes in BRCA. NF-YAs is associated with a proliferative signature, but high levels of NF-YAl signal loss of epithelial features, EMT and acquisition of a more aggressive behavior in a subset of Claudinlow Basal-like tumors.
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Yazdi, Aazam Sadat Heydari, Mahboubeh Eslamzadeh, Bita Najjari, Maryam Emadzadeh, Zhaleh Feyzi, Farzaneh Modaresi, Sara Mirzaeian e Fatemeh Behdani. "Evaluation of Mental Health Status of the Pregnant Women Working in Hospitals during Covid-19 Era: a cross-sectional study". Current Womens Health Reviews 19 (21 ottobre 2022). http://dx.doi.org/10.2174/1573404819666221021085739.
Abstract (sommario):
Background: Many of women and pregnant women are front-line health care workers in the COVID-19 era and are worried about the possible impacts of COVID-19 on their fetus. Due to the pressure and high working load on the healthcare workers during the COVID-19 crisis, the healthcare workers were potentially at risk of different types of mental health disorders. Objective: We aimed to evaluate the correlation between mental health status and the level of COVID-19 related anxiety in pregnant healthcare workers in the COVID-19 era in Iran from August 2020 to December 2020. Methods: This cross-sectional study included 64 pregnant clinical residents, general physicians, nurses and other medical staff who worked in the hospitals in Iran, from August 2020 to December 2020 using an anonymous online survey available on Google Form platform. The online survey consisted of socio-demographic questions, pregnancy-related questions, and questions about medical/drug history. The Persian versions of General Health Questionnaire – 28 [GHQ-28], and Corona Disease Anxiety Scale [CDAS] were also filled by the participants. Results: The mean age and gestational age of the participants were 31.3±3.9 years, and 24.5±10.1 weeks respectively. Psychological problems were moderate [total score GHQ-28> 40] in 9.4% [n: 6] of the pregnant healthcare workers. The frequency of moderate/severe problems in the four subclasses, including somatic symptoms, anxiety/insomnia, social dysfunction, and depression were 9[14.1%], 25[39.0%], 7[10.9%], and 10[15.6%], respectively. According to CDAS, 26.5% of participants had moderate to severe COVID-19 related anxiety. COVID-19 related anxiety and its subclasses, physical and psychological, were significantly correlated with GHQ-28 total score and its subclasses, including somatic symptoms, anxiety/insomnia, social dysfunction, and depression among pregnant health care workers [P<0.01]. Conclusion: According to the results of the current study, over 25% of the pregnant health care workers have moderate to severe COVID-19 related anxiety; so, it is crucial for policymakers to focus on the mental health of the pregnant health care workers during the COVID-19 pandemic.
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Vishnu, Abhishek, Chol Shin, J. David Curb, Rachel H. Mackey, Emma Barinas-Mitchell, Kamal Masaki, Aiman El-Saed et al. "Abstract P303: Differential Association of Carotid-femoral, Brachial-ankle, and Femoral Ankle Pulse Wave Velocity (PWV) With Lipoprotein Distributions From The Era Jump Study". Circulation 125, suppl_10 (13 marzo 2012). http://dx.doi.org/10.1161/circ.125.suppl_10.ap303.
Abstract (sommario):
Objectives: We have previously reported that brachial-ankle PWV (baPWV) is more strongly related to lipoprotein subclasses than carotid-femoral PWV (cfPWV) among middle-aged white men. The current study examined the associations of baPWV, cfPWV and femoral ankle PWV (faPWV) with lipoprotein subclasses in Japanese Americans, Koreans, and Whites. Methods: The ERA JUMP Study is an international population-based study of subclinical atherosclerosis in men aged 40-49 without clinical CVD in the US, Korea, Hawaii and Japan. Participants for the current study were 310 whites, 303 Japanese Americans and 302 Koreans. PWV was assessed using an automated waveform analyzer (VP2000, Omron, Japan). Lipoprotein subclasses were assessed by NMR lipoproteins. Multiple linear regressions were performed to analyze the association of each PWV with NMR lipoprotein distributions after adjusting for age, body mass index, systolic blood pressure, and other potential confounders. Results: Both baPWV and faPWV had significant association with total, large, and small LDL-P after adjusting for race and other confounders, and across three racial groups except for faPWV in whites ( Table ). cfPWV had also significant associations with total and small LDL-P after adjusting for race and other confounders but these associations were weaker than those with baPWV and faPWV. Similarly, both baPWV and faPWV had significant associations with VLDL-P (total, large and small VLDL-P) and HDL-P (total, large, medium, and small HDL-P) but the associations of cfPWV with these lipoproteins were weaker and mostly non-significant. Conclusions: As compared to cfPWV, both baPWV and faPWV had stronger associations with lipoprotein distributions across three racial groups with very different lifestyle. Our results suggest that baPWV and faPWV are more related to atherosclerosis than cfPWV whereas cfPWV may represent arteriosclerosis. Table 1. Association between LDL subclasses(LDL-P) and carotid-femoral, brachial-ankle and femoral-ankle pulse wave velocities among young men in Korea, Hawaii and North America: Multiple linear regression derived beta (β) values (SE) @ Large LDL Small LDL Total LDL Particles cfPWV All participants $ −0.074 (.050) 0.405 (.204) * 0.152 (.072) * Whites −0.045 (.081) 0.442 (.309) 0.197 (.094) * Koreans −0.179 (.084) * 1.143 (.375) ** 0.337 (.140) * Japanese Americans 0.060 (.98) 0.064 (.361) 0.016 (.151) faPWV All participants $ −0.252 (.067) *** 1.201 (.264) *** 0.331 (.099) *** Whites 0.007 (.100) 0.368 (.389) 0.165 (.122) Koreans −0.252 (.113) * 1.609 (.502) ** 0.472 (.189) * Japanese Americans −0.501 (.152) ** 2.266 (.552) *** 0.698 (.225) ** baPWV All participants $ −0.310 (.053) *** 1.334 (.210) *** 0.404 (.075) *** Whites −0.212 (.108) * 1.220 (.415) ** 0.425 (.131) ** Koreans −0.245 (.079) ** 1.398 (.351) *** 0.493 (.126) *** Japanese Americans −0.194 (.098) * 1.132 (.357) ** 0.392 (.143) ** * p<0.05, ** p<0.01, *** p<0.001 # After excluding participants with diabetes mellitus, and those taking medicines for diabetes mellitus, hypertension and hyperlipidemia, number of participants were 248 Whites, 262 Koreans and 192 Japanese Americans. @ Adjusted for age, systolic blood pressure, body mass index, fasting glucose, pack-years smoking, alcohol intake and LDL cholesterol. $ Additionally adjusting for race.
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Oustry, Patricia, Agnès Estival, Lucien Pradayrol, Nicole Vaysse e François Clémente. "Two subclasses of EGF receptors in the human pancreatic cancer cell lines CAPAN-1 and MIA PaCa-2". International Journal of Pancreatology 6, n. 2 (marzo 1990). http://dx.doi.org/10.1007/bf02933046.
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Cai, Jiajia, Jianyun Chen, Ling Huang, Changxi Wang, Weiyun Zhang, Quan Zhou e Zhaohui Sun. "A TIMM17A Regulatory Network Contributing to Breast Cancer". Frontiers in Genetics 12 (5 agosto 2021). http://dx.doi.org/10.3389/fgene.2021.658154.
Abstract (sommario):
BackgroundTranslocase of inner mitochondrial membrane 17A (TIMM17A) is overexpressed in breast cancer (BRCA), and upregulation can increase the aggressiveness of BRCA cells. This study examined the influence of the TIMM17A gene network on BRCA outcome.MethodsExpression levels of TIMM17A were compared between normal and tumor tissues from the OncomineTM database, and the association with patient survival was analyzed using Kaplan–Meier Plotter. Clinical factors influencing TIMM17A expression were studied by UALCAN. cBioPotal was then used to identify genes interacting with TIMM17A, and network relationships were assessed using the R clusterProfiler package. The association between TIMM17A mutation and mRNA expression in BRCA was examined using the LinkFinder application in LinkedOmics, and coexpressed genes were assessed for functional enrichment using the LinkInterpreter application. Furthermore, TIMM17A expression correlation with cell cycle phase distribution was performed by flow cytometry. Finally, the target networks of kinases, microRNAs (miRNAs), and transcription factors were identified using GeneMANIA. The expression and correlation of potential miRNAs and targets were further validated in BRCA cell lines by qRT-PCR.ResultsExpression of TIMM17A was significantly elevated in BRCA compared with normal tissue (p < 0.05), and overexpression was associated with both poor overall survival (OS) and shorter distant metastasis-free survival (DMFS) (p < 0.05). Expression of TIMM17A was not associated with age, sex, BRCA subclass, clinical stage, or patient ethnicity. The coexpressed TIMM17A network was enriched in genes targeted by cell cycle regulators such as CDK1, miR-331, and E2F family transcription factors (FDR < 0.001). Furthermore, flow cytometry revealed a strong association between higher TIMM17A expression and faster cell cycle progression in these BRCA cell lines. In addition, expression of TIMM17A protein was correlated with CDK1 protein expression in BRCA cell lines as measured by western blotting.ConclusionElevated TIMM17A expression accelerates the progression of BRCA, thereby reducing OS and DMFS. The TIMM17A-associated networks identified here provide clues to the molecular pathogenesis of BRCA and potential targets for BRCA treatment.
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Nicholson, Tracy L., Anwar A. Kalalah e Mark Eppinger. "Population structure and genetic diversity of Streptococcus suis isolates obtained from the United States". Frontiers in Microbiology 14 (21 settembre 2023). http://dx.doi.org/10.3389/fmicb.2023.1250265.
Abstract (sommario):
Diseases caused by the zoonotic pathogen Streptococcus suis are an extensive economic problem as well as an animal welfare concern for the global swine industry. Previous studies have evaluated the genomic diversity and population structure of S. suis isolates, however, the majority of these studies utilized isolates obtained from countries other than the U.S. This study applied whole genome sequencing and cgMLST-based typing to evaluate the population structure and genetic relatedness among S. suis isolates obtained within the U.S. The established high-resolution phylogenomic framework revealed extensive genomic variation and diversity among the sampled S. suis isolates, with isolates from the U.S. and from countries outside the U.S. found interspersed in the phylogeny. S. suis isolates obtained within the U.S. did not cluster by state or geographic location, however, isolates with similar serotypes, both obtained from within and outside the U.S., generally clustered together. Average nucleotide identity (ANI) values determined for the S. suis genomes were extensively broad, approaching the recommended species demarcation value, and correlated with the phylogenetic group distribution of the cgMLST-based tree. Numerous antimicrobial resistance (AMR) elements were identified among both U.S. and non-U.S. isolates with ble, tetO, and ermB genes identified as the most prevalent. The epf, mrp, and sly genes, historically used as markers for virulence potential, were also observed in the genomes of isolates that grouped together forming a subclade of clonal complex 1 (CC1) isolates. Collectively, the data in this report provides critical information needed to address potential biosurveillance needs and insights into the genetic diversity and population structure of S. suis isolates obtained within the U.S.
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Lobao, Antonio, Abbas Smiley e Rifat Latifi. "Longer Hospital Length of Stay and Emergency Surgical Intervention are Associated with Lower Rates of Mortality In Elderly Patients with Ruptured Abdominal Aortic Aneurysm: An Analysis of 7,214 Patients". Surgical Technology Online 41 (5 settembre 2022). http://dx.doi.org/10.52198/22.sti.41.gs1625.
Abstract (sommario):
Introduction: We aimed to determine predictors for in-hospital mortality for elderly patients with ruptured abdominal aortic aneurysms (AAA) undergoing emergency admission. Materials and Methods: This was a retrospective cohort study utilizing the National Inpatient Sample (NIS) Database, 2005–2014, on elderly patients with ruptured AAA undergoing emergency admission. ICD-9 code 441.3 was used to identify patients with ruptured AAA. Male versus female sex, survived versus deceased patients, and operated versus not-operated ones were compared for various patient characteristics. A multivariable logistic regression with backward elimination and a generalized additive model (GAM) were implemented to evaluate the associations between potential risk factors and mortality. Results: A total of 7,214 patients aged 65 and older with ruptured AAA were included. About 31% of total sample, 26% of survived, and 36% of deceased were female. Mortality rate was higher in older patients, females, and those who were not operated on (40.6%) versus those that were (74.5%). Age, sex, healthcare insurance, severity of illness subclass, hospital length of stay, total charges, and several comorbidities had significant association with mortality in univariable models. Multivariable logistic regression with backward elimination confirmed age (odds ratio[OR]=1.04; 95% confidence interval [CI]=1.03–1.05; p<0.001), sex (OR=1.23; 95%CI=1.07–1.41; p=0.004), hospital length of stay (OR=0.87; 95%CI=0.86–0.88; p<0.001), bacterial infection (OR=3.79; 95%CI=3.07–4.68; p<0.001), cardiac disease (OR=1.97; 95%CI=1.71–2.28; p<0.001), liver disease (OR=2.90; 95%CI=2.22–3.77; p<0.001), fluid and electrolyte disorders (OR=1.34; 95%CI=1.18–1.52; p<0.001), and coagulopathy (OR=1.96; 95%CI=1.04–1.37; p=0.01) to be the independent predictors of mortality. Age showed a linear association with mortality; whereas, hospital length of stay had a significant L-shaped association. Elderly patients emergently admitted for ruptured AAA had the lowest risk of mortality with hospital stays greater than seven days (EDF=13.91, p<0.0001). Conclusion: Longer hospital length of stay (>7 days) of emergently admitted elderly patients with ruptured abdominal aortic aneurysm was associated with better outcomes and lower risk of mortality. Surgical intervention was also associated with much lower rate of mortality, while increasing age was associated with higher rate of mortality. In elderly patients admitted for ruptured abdominal aortic aneurysm, every one year older than 65, increased the odds of mortality by 4% and female sex increased the odds of mortality by 23%.