170,197 research outputs found
Exploring the mitochondrial degradome by the TAILS proteomics approach in a cellular model of Parkinson’s disease
Abstract
Among neurodegenerative diseases, Parkinson's disease (PD) is the second most frequent
worldwide. PD is primarily characterized by the specific loss of nigral dopaminergic neurons,
accompanied by the onset of cardinal motor symptoms [1]. Mitochondrial dysfunction appears to
have a major contribution in neuron cells death [2,3]. Dopaminergic neurons are more sensitive
to mitochondrial dysfunction than other neuron types since dopamine (DA) itself can undergo
spontaneous oxidation when not correctly stored in acidic vesicles, thus fostering mitochondrial
damage and oxidative stress [4]. A highly conserved system of mitochondrial proteases provides
a tool to ensure the maintenance of proper mitochondrial proteins activity [5]. Hence, the use of
a proteomics approach to study the complete repertoire of mitochondrial proteases (i.e.,
mitochondrial degradome) and their protein targets, in cellular models mimicking early
pathogenetic events in PD, represents a great chance for the discovery of new candidate disease
biomarkers.
The human neuroblastoma SH-SY5Y cell line is widely used as a cellular model to study PD
pathogenesis, since a marked increase in the cytoplasmic DA concentration can be reached upon
the addition of DA to the culture medium. Using this model, we have recently collected evidence
supporting the hypothesis of DA-induced activation of mitochondrial proteases [6-8].
A procedure termed TAILS (Terminal Amine Isotopic Labeling of Substrates) has been recently
designed for degradomics analysis [9]. In the present work, we re-adapted the TAILS protocol to
our specific aim, which is a comprehensive characterization of mitochondrial proteases and their
substrates in a cellular model of altered DA homeostasis in SH-SY5Y cells, which mimics the
early steps in PD pathogenesis. To this aim, SH-SY5Y cells were treated with DA (0.25 mM, 24
hours), mitochondria-enriched fractions were isolated and the TAILS bench protocol was
performed as described by Overall and coworkers [9].
As results, we identified so far 62 peptides whose presence and abundance is influenced by
dopamine. Among these, we found an interesting proteolytic peptide overexpressed in DA-treated
cells, belonging to the mitochondrial 39S ribosomal protein L49. Using the MEROPS database,
we have matched the cleavage site with that of a candidate protease, named neprilysin, that has
been already associated to neurodegeneration because of its ability to degrade the amyloid beta
peptide
From Macrocyclic ligands to fluorescent molecular sensors for metal ions: recent results and perspectives
Hg2+ detection by new anthracene pendant-arm derivatives of mixed N/S- and N/S/O-donor macrocycles: fluorescence, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and density functional theory studies
The optical response of four new anthracenylmethyl pendant-arm derivatives (L1-L4) of the macrocyclic ligands [12]aneNS(3), [12]aneNS(2)O, [15]aneNS(2)O(2), and [12]aneN(2)SO toward the metal ions Zn(2+), Cd(2+), Pb(2+), Cu(2+), Hg(2+), Ag(+), Fe(2+), Co(2+), Ni(2+), Mn(2+), Ca(2+), Na(+), Mg(2+), and K(+) was investigated in 1:1 (v/v) MeCN/H(2)O solutions. A strong chelation enhancement of quenching effect was observed on the fluorescent emission intensity of L2 as a consequence of the host-guest interaction with Hg(2+) and the formation of a 1:2 metal-to-ligand complex. Density functional theory calculations confirmed the formation of a sandwich-type complex between L2 and Hg(2+) as a favorable process. A matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry study using the four ligands as active MALDI probes was also performed. L1-L4 have also been explored as fluorescence chemosensors in microsamples using NANODROP technology
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Multistate/Multifunctional Behaviour of 4’-Hydroxy-6-nitroflavylium: a Write-Lock/Read/Unlock/Enable-Erase Cycle Driven by Light and pH stimulation
Removal of inorganic mercury from aqueous solutions by biomass of the marine macroalga Cystoseira baccata
The ability of Cystoseira baccata algal biomass to remove Hg(II) from aqueous solutions is investigated. The mercury biosorption process is studied through batch experiments at 25 degrees C with regard to the influence of contact time, initial mercury concentration, solution pH, salinity and presence of several divalent cations. The acid-base properties of the alga are also studied, since they are related to the affinity for heavy metals. The studies of the pH effect on the metal uptake evidence a sharp increasing sorption up to a pH value around 7.0, which can be ascribed to changes both in the inorganic Hg(II) speciation and in the dissociation state of the acid algal sites. The sorption isotherms at constant pH show uptake values as high as 178 mg g-1 (at pH 4.5) and 329 mg g-1 (at pH 6.0). The studies of the salinity influence on the Hg(II) sorption capacity of the alga exhibit two opposite effects depending on the electrolyte added; an increase in concentration of nitrate salts (NaNO3, KNO3) Slightly enhances the metal uptake, on the contrary, the addition of NaCl salt leads to a drop in the sorption. The addition of different divalent cations to the mercury solution, namely Ca2+, Mg2+, Zn2+, Cd2+, Pb2+ and Cu2+, reveals that their effect on the uptake process is negligible. Finally, the equilibrium sorption results are compared with predictions obtained from the application of a simple competitive chemical model, which involves a discrete proton binding constant and three additional constants for the binding of the main neutral inorganic Hg(II) complexes, HgCl2, HgOHCl and Hg(OH)2, to the algal surface sites
Mitomycin C in highly myopic eyes - Author reply
Ophthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Synthesis and Structural Characterization of Branched Bimetallic AuPd Nanoparticles with a Highly Tunable Optical Response
Funding Information:
The authors thank the financial support by the PROTEOMASS Scientific Society (Portugal) (General Funding Grant 2023). The authors acknowledge funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant 823717-ESTEEM3, and Ana B. Hungría thanks the financial support from Junta de Andalucía Project P20_00968.
Javier Fernández-Lodeiro thanks FCT for the research contract through the Program DL 57/2016-Norma Transitória. The work was carried out partially through the INL User Facilities (Braga, Portugal) and the Electron Microscope Division (DME) of the Servicios Centrales de Investigación Científica y Tecnológica (SC-ICYT) at Cadiz University (Cadiz, Spain). The authors thank Dr. Jamila Djafari for the assistance with the design of the graphical abstract.
Funding Information:
This work received financial support from Portugal national funds [Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES)] through the Projects UIDB/50006/2020 and UIDP/50006/2020. Silvia Nuti, Carlos Lodeiro, José-Luis Capelo-Martinez, Adrián Fernández-Lodeiro, and Javier Fernández-Lodeiro thank the financial support from national funds (FCT/MCTES) through Project Met4Cat (EXPL/QUI-COL/0263/2021). The authors thank the financial support by the PROTEOMASS Scientific Society (Portugal) (General Funding Grant 2023). The authors acknowledge funding from the European Union’s Horizon 2020 Research and Innovation Program under Grant 823717-ESTEEM3, and Ana B. Hungría thanks the financial support from Junta de Andalucía Project P20_00968. Silvia Nuti thanks FCT/MCTEC (Portugal) for her doctoral grant associated with the chemistry Ph.D. program (SFRH/BD/144618/2019). Javier Fernández-Lodeiro thanks FCT for the research contract through the Program DL 57/2016–Norma Transitória. The work was carried out partially through the INL User Facilities (Braga, Portugal) and the Electron Microscope Division (DME) of the Servicios Centrales de Investigación Científica y Tecnológica (SC-ICYT) at Cadiz University (Cadiz, Spain). The authors thank Dr. Jamila Djafari for the assistance with the design of the graphical abstract.
Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.Bimetallic nanostructures composed of gold (Au) and palladium (Pd) have garnered increased interest for their applications in heterogeneous catalysis. This study reports a simple strategy for manufacturing Au@Pd bimetallic branched nanoparticles (NPs), which offer a tunable optical response, using polyallylamine-stabilized branched AuNPs as template cores for Pd overgrowth. The palladium content can be altered by manipulating the concentration of PdCl42- and ascorbic acid (AA) that are injected, which permit an overgrowth of the Pd shell up to ca. 2 nm thick. The homogeneous distribution of Pd at the surfaces of Au NPs can be carried out regardless of their size or branching degree, which allows for an adjustment of the plasmon response in the near-infrared (NIR) spectral range. As a proof of concept, the nanoenzymatic activity of pure gold and gold-palladium NPs was compared, exploring their peroxidase-like activity in the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). The bimetallic AuPd NPs demonstrate an increase in the catalytic properties attributed to the presence of palladium at the surface of gold.publishersversionpublishe
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Hg2+ detection by new anthracene pendant-arm derivatives of mixed N/S-, and N/S/O-donor macrocycles: Fluorescence, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and DFT studies
The optical response of four new anthracenylmethyl pendant-arm derivatives (L1-L4) of the macrocyclic ligands
[12]aneNS3, [12]aneNS2O, [15]aneNS2O2, and [12]aneN2SO toward the metal ions Zn(II, Cd(II),Pb(II), Cu(II),Hg(II),
Ag(I),Fe(II),Co(II),Ni(II),Mn(II)Ca(II),Na(I),Mg(II)
, and K(I)
was investigated in 1:1 (v/v) MeCN/H2O solutions. A strong
chelation enhancement of quenching effect was observed on the fluorescent emission intensity of L2 as a consequence
of the host-guest interaction with Hg(II)
and the formation of a 1:2 metal-to-ligand complex. Density
functional theory calculations confirmed the formation of a sandwich-type complex between L2 and Hg(II) as a
favorable process. A matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry study using
the four ligands as active MALDI probes was also performed. L1-L4 have also been explored as fluorescence
chemosensors in microsamples using NANODROP technology
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