Exploiting Principal Component Analysis (PCA) to reveal temperature, buffer and metal ions' role in neuromelanin (NM) synthesis by dopamine (DA) oxidative polymerization.

Neuromelanin (NM) plays a well-established role in neurological disorders pathogenesis; the mechanism of action is still discussed and the investigations in this field are limited by NM's complex and heterogeneous composition, insolubility, and low availability from human brains. An alternative can be offered by synthetic NM obtained from dopamine (DA) oxidative polymerization; however, a deep knowledge of the influence of both physicochemical parameters (T, pH, ionic strength) and other compounds in the reaction media (buffer, metal ions, other catecholamines) on DA oxidation process and, consequently, on synthetic NM features is mandatory to develop reliable NM preparation methodologies. To partially fulfill this aim, the present work focuses on defining the role of temperature, buffer and metal ions on both DA oxidation rate and DA oligomer size.

Asymmetric Sulfoxidation by a Tyrosinase Biomimetic Dicopper Complex with a Benzimidazolyl Derivative of L-Phenylalanine.

A challenge in mimicking tyrosinase activity using model compounds is to reproduce its enantioselectivity. Good enantioselection requires rigidity and a chiral center close to the active site. In this study, the synthesis of a new chiral copper complex, [Cu(mXPhI)], based on an -xylyl-bis(imidazole)-bis(benzimidazole) ligand containing a stereocenter with a benzyl residue directly bound on the copper chelating ring, is reported.

Interaction studies of oxindole-derivatives with β-amyloid peptides inhibiting its aggregation induced by metal ions.

Some hydrazones and Schiff bases derived from isatin, an endogenous oxindole formed in the metabolism of tryptophan, were obtained to investigate their effects on in vitro aggregation of β-amyloid peptides (Aβ), macromolecules implicated in Alzheimer's disease. Some hydrazone ligands, prepared by condensation reactions of isatin with hydrazine derivatives, showed a large affinity binding to the synthetic peptides Aβ, particularly to Aβ. Measurements by NMR spectroscopy indicated that those interactions occur mainly at the metal binding site of the peptide, involving His6, His13, and His14 residues, and that hydrazone E-diastereoisomer interacts preferentially with the amyloid peptides.

Interaction and Redox Chemistry between Iron, Dopamine, and Alpha-Synuclein C-Terminal Peptides.

α-Synuclein (αS), dopamine (DA), and iron have a crucial role in the etiology of Parkinson's disease. The present study aims to investigate the interplay between these factors by analyzing the DA/iron interaction and how it is affected by the presence of the C-terminal fragment of αS (Ac-αS) that represents the iron-binding domain. At high DA:Fe molar ratios, the formation of the [Fe(DA)] complex prevents the interaction with αS peptides, whereas, at lower DA:Fe molar ratios, the peptide is able to compete with one of the two coordinated DA molecules.

The novel two-component system AmsSR governs alternative metabolic pathway usage in .

In this study, we identify a novel two-component system in (herein named AmsSR for regulator of alternative metabolic systems) only present in select gammaproteobacterial and betaproteobacterial species. Bioinformatic analysis revealed that the histidine kinase, AmsS, contains 14 predicted N-terminal transmembrane domains and harbors a hybrid histidine kinase arrangement in its C-terminus. Transcriptional analysis revealed the proton ionophore CCCP selectively induces P expression.

Open data for assessing habitats degree of conservation at plot level. An example dataset of forest structural attributes in Val d'Agri (Basilicata, Southern Italy).

Forests supply multiple ecosystem services and host a large proportion of the Earth's terrestrial biodiversity. In particular, they provide habitats for many taxonomic groups which can be threatened by forest unsustainable management practices. Type and intensity of forest management are widely recognized as the main drivers of structure and functions in forests ecosystems.

Copper Binding and Redox Activity of α-Synuclein in Membrane-Like Environment.

α-Synuclein (αSyn) constitutes the main protein component of Lewy bodies, which are the pathologic hallmark in Parkinson's disease. αSyn is unstructured in solution but the interaction of αSyn with lipid membrane modulates its conformation by inducing an α-helical structure of the -terminal region. In addition, the interaction with metal ions can trigger αSyn conformation upon binding and/or through the metal-promoted generation of reactive oxygen species which lead to a cascade of structural alterations.

DOPA pheomelanin is increased in nigral neuromelanin of Parkinson's disease.

Neuromelanin (NM) in dopaminergic neurons of human substantia nigra (SN) has a melanic component that consists of pheomelanin and eumelanin moieties and has been proposed as a key factor contributing to dopaminergic neuron vulnerability in Parkinson's disease (PD). While eumelanin is considered as an antioxidant, pheomelanin and related oxidative stress are associated with compromised drug and metal ion binding and melanoma risk. Using postmortem SN from patients with PD or Alzheimer's disease (AD) and unaffected controls, we identified increased L-3,4-dihydroxyphenylalanine (DOPA) pheomelanin and increased ratios of dopamine (DA) pheomelanin markers to DA in PD SN compared to controls.

Role of the Cysteine in R3 Tau Peptide in Copper Binding and Reactivity.

Tau is a widespread neuroprotein that regulates the cytoskeleton assembly. In some neurological disorders, known as tauopathies, tau is dissociated from the microtubule and forms insoluble neurofibrillary tangles. Tau comprises four pseudorepeats (R1-R4), containing one (R1, R2, R4) or two (R3) histidines, that potentially act as metal binding sites.

Neuromelanins in brain aging and Parkinson's disease: synthesis, structure, neuroinflammatory, and neurodegenerative role.

Neuromelanins are compounds accumulating in neurons of human and animal brain during aging, with neurons of substantia nigra and locus coeruleus having the highest levels of neuromelanins. These compounds have melanic, lipid, peptide, and inorganic components and are contained inside special autolysosomes. Neuromelanins can participate in neuroprotective or toxic processes occurring in Parkinson's disease according to cellular environment.

Water-Soluble Melanin-Protein-Fe/Cu Conjugates Derived from Norepinephrine as Reliable Models for Neuromelanin of Human Brain Locus Coeruleus.

Water-soluble melanin-protein-Fe/Cu conjugates derived from norepinephrine and fibrillar β-lactoglobulin are reliable models for neuromelanin (NM) of human brain locus coeruleus. Both iron and copper promote catecholamine oxidation and exhibit strong tendency to remain coupled in oligonuclear aggregates. The Fe-Cu clusters are EPR silent and affect the H NMR spectra of the conjugates through a specific sequence of signals.

Diversity of European habitat types is correlated with geography more than climate and human pressure.

Habitat richness, that is, the diversity of ecosystem types, is a complex, spatially explicit aspect of biodiversity, which is affected by bioclimatic, geographic, and anthropogenic variables. The distribution of habitat types is a key component for understanding broad-scale biodiversity and for developing conservation strategies. We used data on the distribution of European Union (EU) habitats to answer the following questions: (i) how do bioclimatic, geographic, and anthropogenic variables affect habitat richness? (ii) Which of those factors is the most important? (iii) How do interactions among these variables influence habitat richness and which combinations produce the strongest interactions? The distribution maps of 222 terrestrial habitat types as defined by the Natura 2000 network were used to calculate habitat richness for the 10 km × 10 km EU grid map.

c-di-AMP Is Essential for the Virulence of .

Second messenger nucleotides are produced by bacteria in response to environmental stimuli and play a major role in the regulation of processes associated with bacterial fitness, including but not limited to osmoregulation, envelope homeostasis, central metabolism, and biofilm formation. In this study, we uncovered the biological significance of c-di-AMP in the opportunistic pathogen Enterococcus faecalis by isolating and characterizing strains lacking genes responsible for c-di-AMP synthesis () and degradation ( and ). Using complementary approaches, we demonstrated that either complete loss of c-di-AMP (Δ strain) or c-di-AMP accumulation (Δ, Δ, and Δ Δ strains) drastically impaired general cell fitness and virulence of E.

Oxidase Reactivity of Cu Bound to -Truncated Aβ Peptides Promoted by Dopamine.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino-terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ] and [Cu-Aβ] complexes toward dopamine and other catechols.

Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models.

Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics.

Soft mode theory of ferroelectric phase transitions in the low-temperature phase.

Historically, the soft mode theory of ferroelectric phase transitions has been developed for the high-temperature (paraelectric) phase, where the phonon mode softens upon decreasing the temperature. In the low-temperature ferroelectric phase, a similar phonon softening occurs, also leading to a bosonic condensation of the frozen-in mode at the transition, but in this case the phonon softening occurs upon increasing the temperature. Here we present a soft mode theory of ferroelectric and displacive phase transitions by describing what happens in the low-temperature phase in terms of phonon softening and instability.

Physics of phonon-polaritons in amorphous materials.

The nature of bosonic excitations in disordered materials has remained elusive due to the difficulties in defining key concepts such as quasi-particles in the presence of disorder. We report on an experimental observation of phonon-polaritons in glasses, including a prominent boson peak (BP), i.e.

A Cu-bis(imidazole) Substrate Intermediate Is the Catalytically Competent Center for Catechol Oxidase Activity of Copper Amyloid-β.

Interaction of copper ions with Aβ peptides alters the redox activity of the metal ion and can be associated with neurodegeneration. Many studies deal with the characterization of the copper binding mode responsible for the reactivity. Oxidation experiments of dopamine and related catechols by copper(II) complexes with the N-terminal amyloid-β peptides Aβ and Aβ, and the Aβ[H6A] and Aβ[H13A] mutant forms, both in their free amine and N-acetylated forms show that efficient reactivity requires the oxygenation of a Cu-bis(imidazole) complex with a bound substrate.

Condition-Dependent Coordination and Peroxidase Activity of Hemin-Aβ Complexes.

The peroxidase activity of hemin-peptide complexes remains a potential factor in oxidative damage relevant to neurodegeneration. Here, we present the effect of temperature, ionic strength, and pH relevant to pathophysiological conditions on the dynamic equilibrium between high-spin and low-spin hemin-Aβ constructs. This influence on peroxidase activity was also demonstrated using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and dopamine (DA) oxidation rate analyses with increasing ratios of Aβ and Aβ (up to 100 equivalents).

Genome wide association studies for japonica rice resistance to blast in field and controlled conditions.

Background: Rice blast, caused by the fungus Pyricularia oryzae, represents the most damaging fungal disease of rice worldwide. Utilization of rice resistant cultivars represents a practical way to control the disease. Most of the rice varieties cultivated in Europe and several other temperate regions are severely depleted of blast resistance genes, making the identification of resistant sources in genetic background adapted to temperate environments a priority.

A grid-based map for the Biogeographical Regions of Europe.

Background: Biogeographical units are widely adopted in ecological research and nature conservation management, even though biogeographical regionalisation is still under scientific debate. The European Environment Agency provided an official map of the European Biogeographical Regions (EBRs), which contains the official boundaries used in the Habitats and Birds Directives. However, these boundaries bisect cells in the official EU 10 km × 10 km grid used for many purposes, including reporting species and habitat data, meaning that 6881 cells overlap two or more regions.

Regulatory networks important for survival of Acinetobacter baumannii within the host.

Acinetobacter baumannii is known for its intrinsic resistance to conventional antibiotic treatment and hypervirulence during infection. This coupled with its extraordinary capacity to survive in myriad harsh environments has led to increasing rates of infection in clinical settings. Numerous studies have characterized the virulence factors and resistance genes in A.

Metallotexaphyrins as MRI-Active Catalytic Antioxidants for Neurodegenerative Disease: A Study on Alzheimer's Disease.

The complex etiology of neurodegeneration continues to stifle efforts to develop effective therapeutics. New agents elucidating key pathways causing neurodegeneration might serve to increase our understanding and potentially lead to improved treatments. Here, we demonstrate that a water-soluble manganese(II) texaphyrin (MMn) is a suitable magnetic resonance imaging (MRI) contrast agent for detecting larger amyloid beta constructs.