Fe(II) formation after interaction of the amyloid <Emphasis Type="Italic">β</Emphasis>-peptide with iron-storage protein ferritin

The interaction of amyloid β-peptide (Aβ) with the iron-storage protein ferritin was studied in vitro. We have shown that Aβ during fibril formation process is able to reduce Fe(III) from the ferritin core (ferrihydrite) to Fe(II). The Aβ-mediated Fe(III) reduction yielded a two-times-higher concentration of free Fe(II) than the spontaneous formation of Fe(II) by the ferritin itself. We suggest that Aβ can also act as a ferritin-specific metallochaperone-like molecule capturing Fe(III) from the ferritin ferrihydrite core. Our observation may partially explain the formation of Fe(II)-containing minerals in human brains suffering by neurodegenerative diseases.     

Genetic diversity of the brown marmorated stink bug <Emphasis Type="Italic">Halyomorpha halys</Emphasis> in the invaded territories of Europe and its patterns of diffusion in Italy

Halyomorpha halys is an invasive stink bug pest originating from East Asia. In Europe, it was first detected in Switzerland in 2004. It is now present in thirteen countries, and seems to be spreading throughout the continent. In Italy, where it has been recorded since 2012, other than being an urban nuisance, it is causing severe damage in commercial fruit orchards. An integrated approach, using current and previous observational data in space and time and molecular information, was used to identify the genetic diversity of this pest in Europe, its invasion history, and the potential pathways of entry and diffusion. The analysis of 1175 bp of mitochondrial DNA cytochrome c oxidase I and II genes (cox1, cox2) led to the identification of twenty previously unknown haplotypes. The European distribution of H. halys is the result of multiple invasions that are still in progress, and, in some cases, it was possible to identify the specific Asian areas of origin. Moreover, secondary invasions could have occurred among European countries by a bridgehead effect. In Italy, the data were more clearly related to their temporal occurrence, allowing for a clearer reading of the patterns of invasion and dispersion. After having successfully established in localized areas, H. halys further expanded its range by an active dispersion process and/or by jump dispersal events due to passive transport. The multiple introductions from different areas of the native range together with the different patterns of diffusion of H. halys, may hamper the pest management strategies for its containment.     

Hydrocaffeic and p-coumaric acids,natural phenolic compounds,inhibit UV-B damage in WKD human conjunctival cells in vitro and rabbit eye in vivo

This paper studied the effect on UV-B ocular damage of 10µm hydrocaffeic acid (HCAF) alone and as a mixture (MIX) (5µm HCAF+5µm p-coumaric acid). Since ocular UV-B damage is mediated by reactive oxygen species, the aim was to test if HCAF and MIX could reduce oxidation damage in human conjunctival cells (WKD) in vitro and in cornea and sclera of rabbits in vivo. After UVB irradiation (44 J/m²) of WKD cells, 8-oxodG levels in DNA were markedly increased and this effect was attenuated by HCAF and MIX. Rabbit eyes were treated by application of HCAF and MIX drops before UV-B exposure (79 J/m²). Corneal and scleral DNA oxidation damage, xanthine-oxidase (XO) activity and malondialdehyde levels (MDA) in corneal tissue and prostaglandin E₂ (PGE₂) in the aqueous humour were reduced by HCAF alone and in combination with p-coumaric acid, showing their potential as a topical treatment against UV-B damage.     

Mitochondrially targeted anti-cancer agents

Cancer is an ever-increasing problem that is yet to be harnessed. Frequent mutations make this pathology very variable and, consequently, a considerable challenge. Intriguingly, mitochondria have recently emerged as novel targets for cancer therapy. A group of agents with anti-cancer activity that induce apoptosis by way of mitochondrial destabilisation, termed mitocans, have been a recent focus of research. Of these compounds, many are hydrophobic agents that associate with various sub-cellular organelles. Clearly, modification of such structures with mitochondria-targeting moieties, for example tagging them with lipophilic cations, would be expected to enhance their activity. This may be accomplished by the addition of triphenylphosphonium groups that direct such compounds to mitochondria, enhancing their activity. In this paper, we will review agents that possess anti-cancer activity by way of destabilising mitochondria and their possible targets. We propose that mitochondrial targeting, in particular where the agent associates directly with the target, results in more specific and efficient anti-cancer drugs of potential high clinical relevance.     

Accumulation of fumonisins B1 and B2 in freshly harvested Brazilian commercial maize at three locations during two nonconsecutive seasons

Fifty-six Brazilian commercial maize cultivars were examined for FB1 and FB2 accumulation after two non-consecutive growing seasons. During the 94/95 growing season 35 cultivars were planted at three locations in the state of S?o Paulo, Brazil. All samples (total of 105) were contaminated (0.10 micro/g-6.58 microg/g FB1 and 0.04 microg/g-2.15 microg/g FB2). During the 97/98 growing season, 8 of the cultivars used during 94/95 and 21 others were replanted at the same locations. All 87 samples were contaminated (1.15 microg/g-43.80 microg/g FB1 and 0.08 microg/g-11.65 microg/g FB2). One cultivar accumulated significantly less fumonisins in all locations during both growing seasons, indicating that some degree of selection may be possible even in climates that favor F. moniliforme (verticillioides) infection of maize. The presence of water surplus in soil from kernel maturity to harvest correlated with concentrations of FB1 in the grain for the 8 cultivars planted during both seasons at three locations. Observed trends indicated that water excesses and deficits from silking to harvest increased fumonisin levels. The difference in the incidence of FB1, FB2, and FB1 + FB2 was significant between growing seasons, planting locations and between cultivars. Neither the level of hybridization, nor the type of endosperm, nor the length of the vegetative cycle showed any effect on the FB1 contamination.     

Structural and functional characterization of the Streptococcus pneumoniae RrgB pilus backbone D1 domain

Streptococcus pneumoniae expresses on its surface adhesive pili, involved in bacterial attachment to epithelial cells and virulence. The pneumococcal pilus is composed of three proteins, RrgA, RrgB, and RrgC, each stabilized by intramolecular isopeptide bonds and covalently polymerized by means of intermolecular isopeptide bonds to form an extended fiber. RrgB is the pilus scaffold subunit and is protective in vivo in mouse models of sepsis and pneumonia, thus representing a potential vaccine candidate. The crystal structure of a major RrgB C-terminal portion featured an organization into three independently folded protein domains (D2-D4), whereas the N-terminal D1 domain (D1) remained unsolved. We have tested the four single recombinant RrgB domains in active and passive immunization studies and show that D1 is the most effective, providing a level of protection comparable with that of the full-length protein. To elucidate the structural features of D1, we solved the solution structure of the recombinant domain by NMR spectroscopy. The spectra analysis revealed that D1 has many flexible regions, does not contain any intramolecular isopeptide bond, and shares with the other domains an Ig-like fold. In addition, we demonstrated, by site-directed mutagenesis and complementation in S. pneumoniae, that the D1 domain contains the Lys residue (Lys-183) involved in the formation of the intermolecular isopeptide bonds and pilus polymerization. Finally, we present a model of the RrgB protein architecture along with the mapping of two surface-exposed linear epitopes recognized by protective antisera.     

Population cytogenetics of aphidicolin-induced fragile sites

Summary Chromosome fragile sites are inducible by aphidicolin in cultured human lymphocytes. To assess the frequency and distribution of these common fragile sites in the general population, a cytogenetic survey was performed on 126 subjects, 59 males and 67 females, whose age ranged from 1 day to 72 years. Common fragile sites, induced by aphidicolin, were widespread and showed a remarkably different sensitivity among individuals; age influenced the overall frequency of fragile sites. Moreover, both age and sex seemed to modulate the expression of specific fragile sites. In our population, the most common fragile sites were: 3p14, 16q23, Xp22, 6q26, 1p31, 4q31, 1p22, 7q22, 2q33, 3q27, 2q31, 7q32, 14q24, 10q22, 5q31, 2q37, 6p21.     

Novel methods improve prediction of species' distributions from occurrence data

Prediction of species' distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence-only data to fit models, and independent presence-absence data to evaluate the predictions. Along with well-established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species' distributions. These include machine-learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species' occurrence data. Presence-only data were effective for modelling species' distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.     

Prolactin induces chitotriosidase expression in human macrophages through PTK,PI3‐K,and MAPK pathways

We previously reported that prolactin (PRL) induces chitotriosidase (CHIT‐1) mRNA expression in human macrophages. In this investigation we determined the signaling pathways involved in CHIT‐1 induction in response to PRL. The CHIT‐1 induction PRL‐mediated was reduced by wortmannin and LY‐294002, inhibitors of phosphatidylinositol 3‐kinase (PI3‐K) and by genistein an inhibitor of protein tyrosine kinase (PTK). Pre‐treatment of macrophages with SB203580, a specific inhibitor of the mitogen‐activated kinases (MAPK) p38, or with U0126, an inhibitor of MAPK p44/42, prevented both basal and exogenous PRL‐mediated CHIT‐1 expression. No significant effects on CHIT‐1 induction PRL‐mediated were observed with a protein kinase C inhibitor (PKC), rottlerin, or with an Src inhibitor, PP2, or with JAK2 inhibitor, AG490. In addition, PRL induced a phosphorylation of AKT that was prevented both by the two MAPK inhibitors SB203580 and U0126 and by the PI3‐K inhibitors wortmannin and LY‐294002. In conclusion, our results indicate that PRL up‐regulated CHIT‐1 expression via PTK, PI3‐K, MAPK, and signaling transduction components. J. Cell. Biochem. 107: 881–889, 2009. © 2009 Wiley‐Liss, Inc.     

Epitope Mapping of a Bactericidal Monoclonal Antibody against the Factor H Binding Protein of Neisseria meningitidis

The factor H binding protein (fHbp) is a 27-kDa membrane-anchored lipoprotein of Neisseria meningitidis that allows the survival of the bacterium in human plasma; it is also a major component of a universal vaccine against meningococcus B.In this study, we used nuclear magnetic resonance spectroscopy, mutagenesis, and in silico modeling to map the epitope recognized by MAb502, a bactericidal monoclonal antibody elicited by fHbp. The data show that the antibody recognizes a conformational epitope within a well-defined area of the immunodominant C-terminal domain of the protein that is formed by two loops connecting different β-strands of a β-barrel and a short α-helix brought in spatial proximity by the protein folding. The identification of the protective epitopes of fHbp is an important factor for understanding the mechanism(s) of an effective immune response and provides valuable guidelines for designing variants of the protein able to induce broadly protective immunity.