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121.
Barbara Eleni Rosato Roberta Marra Vanessa DOnofrio Federica Del Giudice Simone Della Monica Achille Iolascon Immacolata Andolfo Roberta Russo 《International journal of molecular sciences》2022,23(3)
Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells. 相似文献
122.
Mariachiara Zuccarini Patricia Giuliani Valentina Di Liberto Monica Frinchi Francesco Caciagli Vanni Caruso Renata Ciccarelli Giuseppa Mud Patrizia Di Iorio 《International journal of molecular sciences》2022,23(3)
Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the contribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents. 相似文献
123.
Rogman Agnieszka Gancarz Roman Domagalska Beata W. Wilk Kazimiera A. 《Topics in Catalysis》2000,11(1-4):451-460
In this work we present mechanism of the base-catalyzed 2-azaallylic rearrangement in homogeneous media. Detailed 2-azaallylic rearrangement studies have shown that tautomerism of derivatives of benzylidenebenzhydrylamines and N-fluorenylidenebenzylamines is not adequately encomposed by the Hammet equation and the equilibrium constant in the case of studied derivatives depends on the electronic as well as steric factors of the azaallylic system substituents. The presence of steric interactions which influence the equilibrium state has been additionally confirmed by means of crystallographic and molecular mechanics data as well as NOE studies. This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
124.
125.
Cristina Siligardi Monica Montecchi Monia Montorsi Luca Pasquali 《Journal of the American Ceramic Society》2009,92(11):2784-2790
A lead-free frit containing high amount of copper and its glaze conceived for fine porcelain stoneware tiles were investigated. The glazes obtained under industrial firing were studied using X-ray photoelectron spectroscopy, X-ray diffraction, optical and scanning electron microscopy with energy dispersion spectroscopy. The mechanism of the red color formation on the surface was explained. The results indicated that the glaze presents a metallic gloss and iridescent colors on the surface, mainly associated to the formation of CuO crystallites and Cu metallic particles. Moreover, the Cu glaze showed a good chemical durability; this is particularly interesting because commercial Cu frits usually present poor chemical properties. 相似文献
126.
Lucjan Chmielarz Piotr Kutrowski Alicja Rafalska-asocha Roman Dziembaj 《Applied catalysis. B, Environmental》2005,58(3-4):235-244
The selective catalytic oxidation of ammonia to nitrogen (NH3-SCO) has been studied over hydrotalcite derived mixed metal oxides containing Cu, Co, Fe or Ni. XRD, BET, NH3-TPD and TPR techniques were used for catalysts characterization. Results of NH3-SCO were compared with those of selective catalytic reduction of NO with NH3 (NO-SCR). Reaction mechanism was studied by temperature-programmed surface reaction (TPSR) and activity tests with a various contact time. Catalytic performance of the studied samples depends on both kind and loading of transition metals in the mixed metal oxide system. The Cu-containing samples have been found to be the most active catalysts of the NH3-SCO process. Transition metal loading strongly influences distribution of ammonia oxidation products. The highest selectivity to N2 was measured for the catalysts with the lowest transition metal content. 相似文献
127.
Summary By reacting esterification of phenolphtalein with methacrylate chloride, phenolphtalein dimethacrylate was obtained. Based on the results of elemental analysis, FTIR, 1H-NMR and 13C-NMR spectra, the structure of the product was proposed. The dimethacrylate was used as new crosslinker to crosslink poly(methyl methacrylate) (PMMA). The influence of the amount dimethacrylate on the crosslink density and some properties of the crosslinked polymers networks such as swelling, mechanical properties (tensile strength and elongation at break) and thermal stability were examined. 相似文献
128.
Monica Popa Ecaterina Vasilescu Paula Drob Doina Raducanu Jose Maria Calderon Moreno Steliana Ivanescu Cora Vasilescu Silviu Iulian Drob 《Metals and Materials International》2012,18(4):639-645
For an alloy to be suitable for use as an implant material, it must have a low specific weight and Young??s modulus, good mechanical properties that are similar to those of bone, and very good corrosion resistance and biocompatibility. In this study, we have developed a novel Ti-20Nb-10Zr-5Ta alloy that is composed of nontoxic, nonallergenic, corrosion-resistant elements. This alloy has low specific weight and Young??s modulus and good mechanical properties. It has a fine microstructure with a matrix that is mainly composed of the ?? phase and some ?? phase due to recrystallization during cooling. It shows elastoplastic behavior with a fairly linear elastic behavior and low Young??s modulus (59 GPa). In addition, its ultimate tensile strength, 0.2% yield strength, and hardness are higher than those of CP Ti, commercial Ti-6Al-4V, and similar ??-type alloys. It exhibited a very stable passive state and its electrochemical parameters and corrosion and ion release rates were better than those of CP Ti in Ringer??s solutions of different pH values that simulate the severe functional conditions of an implant; this is attributable to the beneficial influence of the alloying elements and to the better protective properties of the coated passive film. 相似文献
129.
Casali M Banta S Zambonelli C Megeed Z Yarmush ML 《Protein engineering, design & selection : PEDS》2008,21(6):395-404
Environmentally responsive proteins and peptides are increasingly finding utility in various engineered systems due to their ability to respond to the presentation of external stimuli. A classic example of this behavior is the influenza hemagglutinin (HA) fusion protein. At neutral pH, HA exists in a non-fusogenic state, but upon exposure to low pH, the conformation of the structure changes to expose a fusogenic peptide. During this structural change, massive rearrangements occur in a subunit of HA (HA2). Crystallography data has shown that a loop of 28 amino acids (residues 54-81) undergoes a dramatic transition from a random coil to an alpha-helix. This segment connects to two flanking helical regions (short and long) to form a long, continuous helix. Here, we report the results of site-directed mutagenesis study on LOOP-36 to further understand the mechanism of this important stimulus-responsive peptide. The conformational transition of a bacterially expressed LOOP-36 was found to be less dramatic than has been previously reported. The systematic mutation of glutamate and histidine residues in the peptide to glutamines (glutamine scanning) did not impact the conformational behavior of the peptide, but the substitution of the glycine residue at position 22 with alanine resulted in significant pH-responsive behavior. Therefore this mutant stimulus-responsive peptide may be more valuable for future protein engineering and bionanotechnology efforts. 相似文献
130.
Martin Hintersteiner Dr. Thierry Kimmerlin Dr. Geraldine Garavel Dr. Thorsten Schindler Dr. Roman Bauer Dr. Nicole‐Claudia Meisner Dr. Jan‐Marcus Seifert Dr. Volker Uhl Dr. Manfred Auer Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(6):994-998
New and improved : The incorporation of a 6‐chlorotryptophan (6‐Cl‐Trp) into a β‐peptide (M)‐314 helix leads to a high‐affinity hDM2 inhibitor, as demonstrated by fluorescence fluctuation analysis at single molecule resolution. When conjugated to penetratin, the newly derived hDM2 binder specifically inhibits tumour cell growth in vitro.