Nickel binding sites in histone proteins

Nickel compounds are well known as human carcinogens, though the molecular events that are responsible for this are not well understood. It has been proposed that a crucial element in the mechanism of carcinogenesis is the binding of Ni(II) ions within the cell nucleus. It is known that DNA polymer binds Ni(II) only weakly, leaving the proteins of the cell nucleus as the likely Ni(II) targets. Being histone proteins the most abundant among them, they can be considered the primary sites for nickel binding. Here we describe the interactions of nickel with histone H4, core tetramer (H3-H4)2 and several peptide fragments which have been selected as the candidates for specific binding sites in the histone octamer. The results allowed us to propose several mechanisms of nickel induced damage resulting from metal coordination, including structural changes of histone proteins, as well as nucleobase oxidation and sequence-specific histone hydrolysis. The aim of the present work is to provide a comprehensive overview of literature dealing with nickel coordination to histone proteins and its link with nickel involvement in toxicity and carcinogenicity

Interaction of divalent cations with protein PARK9

Metals have been shown to play a role in the genesis and development of many neurodegenerative diseases. Park9 encoded protein can protect cells from manganese poisoning, an environmental risk factor for a Parkinson’s disease- like syndrome. Park9 belongs to a family of ATP-ases involved in metal coordination and transportation; familial mutations of this gene may result in early development of PD. We tested two peptide sequences from Park9, -P1D2E3K4H5E6L7- (1) and -F1C2G3D4G5A6N7D8C9G10- (2), for Mn(II), Zn(II) and Cu(II) binding. These fragments are located from 1165 to 1171 and from 1184 to 1193 residues in Park9 sequence, and are highly conserved in a number of organisms, from yeasts to humans. Experiments have been carried out at different pH values and ligand/metal molar ratios with both potentiometric and spectroscopic (NMR, UV-vis) techniques, showing that the three metals are able to effectively bind the examined peptides. Mn(II) and Zn(II) coordination with peptide (1) involves imidazol of His5 and carboxyl γ-O of Asp2, Glu3 and Glu6 residues, in a distorted octahedral geometry, possibly involving bidentate interaction of carboxyl groups; four donor atoms participate in Zn(II) binding, resulting in a tetracoordinated geometry. Mn(II) and Zn(II) coordination involves the two cysteines in peptide (2); Mn(II) accepts additional ligand bonds from D4 and D8 to complete the coordination sphere, together with some water molecules. Details of Cu(II) coordination are under study

Nonlinear asymmetric imaging with AlGaAs metasurface

Nowadays, dielectric metasurfaces are a promising platform in many different research fields such as sensing, lasing, all-optical modulation and nonlinear optics. Among all the different kinds of such thin structures, asymmetric geometries are recently attracting increasing interest. In particular, nonlinear light-matter interaction in metasurfaces constitutes a valid approach for achieving miniaturized control over light. Here, we demonstrate nonlinear asymmetric generation of light in a dielectric metasurface via second harmonic generation. By inverting the illumination direction of the pump, the nonlinear emitted power is modulated by more than one order of magnitude. Moreover, we demonstrate how a properly designed metasurface can generate two completely different images at the second harmonic when the direction of illumination is reversed. Our results may pave the way to important opportunities for the realization of compact nanophotonic devices for imaging applications by densely integrating numerous nonlinear resonators

Apoptosis in spermatozoa of infertile men, clinical correlations

The methods for evaluation of male infertility include not only routine investigations, standardized by the WHO, but also complementary techniques, developed over the last years, in order to improve the predictive value of seminal analysis for natural conception and assisted reproduction. With reference to these new methods, studies suggest that sperm with certain levels of DNA fragmentation serve as a strong predictor of reduced male fertility. We studied subjects who underwent seminal fluid evaluation, because of an infertility condition, at the Department of Biomedical Sciences of the University of Sassari.The samples collected by masturbation were evaluated according to the World Health Organisation (1999).The samples was washed twice in PBS and cytocentrifuged for 10 min at 1800 rpm on polylysine-coated slides that were fixed in methanol at room temperature. The apoptosis was evaluated using the TUNEL (In Situ Cell Death Detection Kit, Fluorescein, Roche, Cat.No. 1 684 795). At fluorescent miscroscopy are counted at least 300 cells. Quantitative evaluation of apoptosis by the TUNEL method confirmed that apoptosis did not seem to be correlated with sperm concentration or morphology; however, we found a higher apoptotic rate in semen from patients affected by andrologic diseases, such as varicocele, than from those with alteration of semen characteristics. Apoptosis analysis might be used in infertile patients in order to understand the etiology of unexplained infertility and to improve therapeutic effectiveness

Role of Antenna Modes and Field Enhancement in Second Harmonic Generation from Dipole Nanoantennas

We study optical second harmonic generation from metallic dipole antennas with narrow gaps. Enhancement of the fundamental-frequency field in the gap region plays a marginal role on conversion efficiency. In the symmetric configuration, i.e., with the gap located at the center of the antenna axis, reducing gap size induces a significant red-shift of the maximum conversion efficiency peak. Either enhancement or inhibition of second-harmonic emission may be observed as gap size is decreased, depending on the antenna mode excited at the harmonic frequency. The second-harmonic signal is extremely sensitive to the asymmetry introduced by gap’s displacements with respect to the antenna center. In this situation, second-harmonic light can couple to all the available antenna modes. We perform a multipolar analysis that allows engineering the far-field SH emission and find that the interaction with quasi-odd-symmetry modes generates radiation patterns with a strong dipolar component

Copper(II) complexes of compartmental ligands: structural and stoichiometric aspects depending upon the anionic group of the copper salt

It has been found that anionic species of metal salts can lead to different geometries and stoichiometries in the synthesis of coordination compounds. Therefore, using the same cation but different polyatomic anion groups such as oxalate, sulfate, acetate, oxamate etc. [1], it is possible to obtain metal complexes with various structural and stoichiometric features upon coordination. In fact, these anionic groups can behave themselves, generally, as mono-, bidentate and bridgedbidentate ligands towards metal ions. In the last years, with the aim to design a multi-dentate ligand capable of supporting simultaneous coordination to three copper atoms and to mimic the multicopper active sites of blue copper oxidases (e.g., laccase, ascorbate oxidase and ceruloplasmin), we focused our studies on the synthesis and structural characterization of copper(II) complexes of compartmental acyclic bis(salicylhydrazone) ligands derived from iminoand methyl-iminodiacetic acid, finding a different behaviour using copper(II) sulfate, perchlorate and acetate salts. Thus, we have obtained, with a 1:3 (ligand-to-metal) molar ratio, a trinuclear coordination polymer from Cu(II) perchlorate [2], a sulfato-bridged hexanuclear dimer [3] and a mononuclear complex using Cu(II) acetate [4]. Microbiological investigations showed a good activity of the sulfato and perchlorato complexes. Studies concerning DNA binding of these compounds are now in progress

Interaction of Cu(II) ions with a fragment of Park9 protein

Parkinson Disease (PD) is a neurodegenerative pathology whose causes have not yet been fully clarified. In this perspective, we have chosen short fragments of Ypk9 protein that include interesting sequences for metal binding and are highly conserved in a number of different organisms, located in domains of the protein readily accessible to the metals. We studied their behaviour towards divalent cations such as manganese and zinc, using NMR mono- and bidimensional techniques and EPR spectroscopy. As this study was going on, we also started the investigation on Cu(II) coordination, showing by a series of potentiometric and spectroscopic measurements that this metal too is able to effectively bind the chosen sequence. Here we would like to report our latest findings

Malattie neurodegenerative e metalli: cosa lega la sindrome di Parkinson al manganese

E' noto come l'accumulo dei metalli nel cervello possa portare, o quantomeno contribuire, allo sviluppo di malattie neurodegenerative, attraverso meccanismi che solo ora cominciano a essere lentamente chiariti. La malattia di Parkinson, cosiddetta “idiopatica” in quanto non presenta alcuna causa apparente, è stata messa di recente in correlazione con l'esposizione o l'avvelenamento da manganese. Studi epidemiologici condotti da diverse università degli Stati Uniti hanno evidenziato come gli abitanti in zone urbane con alte concentrazioni di questo metallo avessero una probabilità di sviluppare il Parkinson quasi due volte più alta rispetto agli abitanti in zone meno inquinate, o inquinate da altri metalli (quali ad esempio il rame). Altri studi apparsi di recente in letteratura correlano l'esposizione al manganese con alcune modificazioni di un gene legato alla sinucleina, proteina presente con diverse funzioni in tutte le malattie neurodegenerative. Lo studio è stato effettuato su una proteina di un lievito la YPK9, al 58% simile e al 38% uguale all'analoga umana PARK9, la cui mutazione causa appunto lo sviluppo di una forma ereditaria di Parkinson. Silenziando il gene YPK9 nei lieviti si è notato che in assenza della relativa proteina questi mostravano disturbi nella crescita se sottoposti all'azione di diversi metalli, mentre in presenza del manganese la crescita era particolarmente ridotta. Veniva quindi dimostrata l'azione protettiva della YPK9 nei confronti dei cationi bivalenti, specialmente del manganese. Pare dunque possibile che una modifica sull'analogo umano, il PARK9, sia in grado di inficiare i normali meccanismi con cui il nostro organismo si protegge da ioni metallici dannosi, quali il manganese, e dando il via a una serie di processi che portano allo sviluppo della malattia neurodegenerativa. Abbiamo pertanto voluto verificare l'effettiva propensione di tale proteina a interagire con ioni Mn(II), selezionando sulla sequenza della YPK9 dei frammenti promettenti per il legame con il metallo e investigando la possibilità di una interazione efficace di questi frammenti con diversi cationi bivalenti, tra cui appunto il manganese, ma anche il calcio e lo zinco. I risultati preliminari, ottenuti attraverso alcune tecniche spettroscopiche quali l'NMR mono- e bidimensionale e l'EPR, verranno esposti in questa comunicazione

Park9 interaction with Manganese and other divalent cations

Two peptide sequences from Park9 Parkinson’s disease gene, P1D2E3K4H5E6L7 (1) and F1C2G3D4G5A6N7D8C9G10 (2) have been studied in their interaction with Mn(II) and Zn(II) ions. These fragments lie from residue 1165 to 1171 and from 1184 to 1193 in the Park9 encoded protein, that can protect cells from manganese poisoning, an environmental risk factor for a Parkinson’s disease-like syndrome called Manganism. The study was carried out through potentiometric and spectroscopic (UV-Vis, EPR, mono- and multidimensional NMR) techniques, to cast light on the details of metal binding at different pH values and different ligand to metal molar ratios

Seeing the wood through the trees. Combining shape information from different landmark configurations

The geometric morphometric (GM) analysis of complex anatomical structures is an ever more powerful tool to study biological variability, adaptation and evolution. Here, we propose a new method (combinland), developed in R, meant to combine the morphological information contained in different landmark coordinate sets into a single dataset, under a GM context. combinland builds a common ordination space taking into account the entire shape information encoded in the starting configurations. We applied combinland to a Primate case study including 133 skulls belonging to 14 species. On each specimen, we simulated photo acquisitions converting the 3D landmark sets into six 2D configurations along standard anatomical views. The application of combinland shows statistically negligible differences in the ordination space compared to that of the original 3D objects, in contrast to a previous method meant to address the same issue. Hence, we argue combinland allows to correctly retrieve 3D-quality statistical information from 2D landmark configurations. This makes combinland a viable alternative when the extraction of 3D models is not possible, recommended, or too expensive, and to make full use of disparate sources (and views) of morphological information regarding the same specimens. The code and examples for the application of combinland are available in the Arothron R package