¿Neurologist's contribution to the diagnosis of sine materia respiratory insufficiency: case report¿

ABSTRACT: Right-to-left shunt (RLS) can be the reason of marked hypoxemia, this diagnosis of respiratory insufficiency is usually difficult to make by Respiratory Physicians as it develops in absence of an intrinsic lung disease. We report a case of RLS in a patient with a hepatopulmonary syndrome caused by chronic autoimmune cholangitis which was suspected clinically by physical examination and by standard CT imaging and MIP reconstruction of the pulmonary vascular bed. Repeated previous transthoracic echocardiography (TTE) studies didn't reveal the shunts. The final diagnosis was performed by a minimally invasive doppler transcranial examination with the use of agitated saline as contrast solution. Transcranial Colour-Coded Duplex Sonography (TCCS) with saline contrast medium injection is described to have an higher sensitivity compared with TTE and comparable with transesophageal echocardiography (TEE) in RLS diagnosis. The collaboration of Neurologists to this diagnosis of respiratory insufficiency is really important, as the examination is simple, well tolerated in comparison with the discomfort associated with transesophageal echocardiography, and of minimal invasivity in comparison with angiography which is the ultimate diagnostic procedure in this clinical scenario. TCCS with saline contrast medium injection, should be performed for the diagnosis of chronic hypoxemia for which causes are not detected with routine clinical examinations, in order to confirm RLS.     

A caged cyanide

A photoactivatable caged cyanide, 1-(2-nitrophenyl)ethyl (NPE) cyanide, was synthesized, which upon irradiation in the near UV releases cyanide. It is demonstrated that the compound can be used to induce formation of the Fe(III)-CN(-) complex in the heme protein nitrophorin 4 from Rhodnius prolixus.     

The chemopreventive role of dietary phytochemicals through gap junctional intercellular communication

Dietary phytochemicals offer protection from oxidative damages and lower the risks of chronic diseases, by complementary and overlapping action mechanisms. These include antioxidant activity, regulation of gene expression and cell cycle, stimulation of the immune and hormonal systems and modulation of cell–cell communication. Gap-junction intercellular communication (GJIC) plays an important role in maintaining tissue homeostasis by allowing the intercellular exchange of ions and regulatory molecules associated with cell proliferation, differentiation and apoptosis, and by contributing to intracellular signaling. This mechanism is strictly regulated and abnormal GJIC can result in several pathological conditions. GJIC is deregulated in cancer cells and reversible GJIC inhibition is strongly related to the promotion phase of carcinogenesis, likely mediated by reactive oxygen species. Whereas, the reversible inhibition of GJIC is related to the promotion phase of carcinogenicity, enhancers of GJIC are expected to prevent cancer. Several dietary plant compounds demonstrated the ability to control GJIC at the epigenetic levels and to prevent GJIC down-regulation by tumor promoting compounds, thus preventing cancers. In this Commentary, a number of reported studies on several phytochemicals in dietary and medicinal plants, which were able to affect GJIC and their structural proteins, i.e., connexins, in different in vivo and in vitro systems, were examined. The growing evidence, on the involvement of plant-derived molecules in the modulation of GJIC and in understanding of the specific action mechanisms, might offer a new perspective of the protective and/or preventive effects of dietary phytochemicals, in addition to possible chemotherapeutic use.     

Origin and patterns of genetic diversity of German fallow deer as inferred from mitochondrial DNA

Although not native to Germany, fallow deer (Dama dama) are commonly found today, but their origin as well as the genetic structure of the founding members is still unclear. In order to address these aspects, we sequenced ~400 bp of the mitochondrial d-loop of 365 animals from 22 locations in nine German Federal States. Nine new haplotypes were detected and archived in GenBank. Our data produced evidence for a Turkish origin of the German founders. However, German fallow deer populations have complex patterns of mtDNA variation. In particular, three distinct clusters were identified: Schleswig-Holstein, Brandenburg/Hesse/Rhineland and Saxony/lower Saxony/Mecklenburg/Westphalia/Anhalt. Signatures of recent demographic expansions were found for the latter two. An overall pattern of reduced genetic variation was therefore accompanied by a relatively strong genetic structure, as highlighted by an overall Phict value of 0.74 (P < 0.001).     

Host-induced gene silencing: a tool for understanding fungal host interaction and for developing novel disease control strategies

Recent discoveries regarding small RNAs and the mechanisms of gene silencing are providing new opportunities to explore fungal pathogen-host interactions and potential strategies for novel disease control. Plant pathogenic fungi are a constant and major threat to global food security; they represent the largest group of disease-causing agents on crop plants on the planet. An initial understanding of RNA silencing mechanisms and small RNAs was derived from model fungi. Now, new knowledge with practical implications for RNA silencing is beginning to emerge from the study of plant-fungus interactions. Recent studies have shown that the expression of silencing constructs in plants designed on fungal genes can specifically silence their targets in invading pathogenic fungi, such as Fusarium verticillioides, Blumeria graminis and Puccinia striiformis f.sp. tritici. Here, we highlight the important general aspects of RNA silencing mechanisms and emphasize recent findings from plant pathogenic fungi. Strategies to employ RNA silencing to investigate the basis of fungal pathogenesis are discussed. Finally, we address important aspects for the development of fungal-derived resistance through the expression of silencing constructs in host plants as a powerful strategy to control fungal disease.     

Differing modes of interaction between monomeric Aβ(1-40) peptides and model lipid membranes: an AFM study

Membrane interactions with β-amyloid peptides are implicated in the pathology of Alzheimer's disease and cholesterol has been shown to be key modulator of this interaction, yet little is known about the mechanism of this interaction. Using atomic force microscopy, we investigated the interaction of monomeric Aβ(1-40) peptides with planar mica-supported bilayers composed of DOPC and DPPC containing varying concentrations of cholesterol. We show that below the bilayer melting temperature, Aβ monomers adsorb to, and assemble on, the surface of DPPC bilayers to form layers that grow laterally and normal to the bilayer plane. Above the bilayer melting temperature, we observe protofibril formation. In contrast, in DOPC bilayers, Aβ monomers exhibit a detergent-like action, forming defects in the bilayer structure. The kinetics of both modes of interaction significantly increases with increasing membrane cholesterol content. We conclude that the mode and rate of the interaction of Aβ monomers with lipid bilayers are strongly dependent on lipid composition, phase state and cholesterol content.     

Monosialoganglioside-GM1 triggers binding of the amyloid-protein salmon calcitonin to a Langmuir membrane model mimicking the occurrence of lipid-rafts

GM1 ganglioside is known to be involved in the amyloid-associated diseases and it is a crucial factor for the assembly of amyloid proteins on lipid-rafts, which are lipid structures located on the synaptic plasma membranes. Due to its slow aggregation rate, we employed salmon calcitonin (sCT) as a suitable probe representative of amyloid proteins, to study the interaction between this class of proteins and a membrane model. Here, we prepared a neuronal membrane model by depositing onto mica two Langmuir-Blodgett films in liquid-condensed phase: the outer monolayer was characterized by high content of GM1 (50%) and minority parts of cholesterol and POPC (25–25%), while the inner one by plain POPC. To deeply investigate the interaction of sCT with this model and the role-played by GM1, we prepared the outer leaflet adding sCT at a concentration such that the number of proteins equals that of GM1. Atomic Force Microscopy revealed the occurrence of two distinct kinds of flat surfaces, with globular aggregates localized exclusively on top of the highest one. To unravel the nature of the interaction, we studied by ζ-potential technique liposomes composed as the outer leaflet of the model. Results demonstrated that an electrostatic interaction sCT-GM1 occurred. Finally, to investigate the interaction thermodynamics between sCT and the outer leaflet, Langmuir films as the outer monolayer and containing increasing content of sCT were studied by compression isotherms and Brewster Angle Microscopy experiments. Based on the all body of results we propose an interaction model where GM1 plays a pivotal role.     

Identification and distribution of chondroitin sulfate in the three electric organs of the electric eel, Electrophorus electricus (L.)

The electrogenic tissue of the electric eel Electrophorus electricus (L.) is distributed in three well-defined electric organs, the Main electric organ, Sach's organ and Hunter's organ. Sulfated glycosaminoglycan (GAG) composition was characterized in the three electric organs of the electric eel. Sulfated GAGs were analyzed in the electric organs using metachromatic staining, biochemical analysis including electrophoresis before and after specific enzymatic or chemical degradations, and immunostaining with an antibody against chondroitin sulfate (CS). Our results showed in the three electric organs that CS was the main sulfated GAG species detected, accompanied by small and diminutive amounts of CS/dermatan sulfate hybrid chains and heparan sulfate (HS), respectively. However, HS was not detected in the Sach's organ. CS was predominantly detected in the innervated membrane face of the electroplaques in the three electric organs. Our findings extend previous observations on the GAG composition in the electric organs of E. electricus and provide new information regarding the tissue distribution and location of CS.     

Unexpected presence of <Emphasis Type="Italic">Fagus orientalis</Emphasis> complex in Italy as inferred from 45,000-year-old DNA pollen samples from Venice lagoon

Background

Phylogeographic analyses on the Western Euroasiatic Fagus taxa (F. orientalis, F. sylvatica, F. taurica and F. moesiaca) is available, however, the subdivision of Fagus spp. is unresolved and there is no consensus on the phylogeny and on the identification (both with morphological than molecular markers) of Fagus Eurasiatic taxa.For the first time molecular analyses of ancient pollen, dated at least 45,000 years ago, were used in combination with the phylogeny analysis on current species, to identify the Fagus spp. present during the Last Interglacial period in Italy.In this work we aim at testing if the trn L-trn F chloroplast DNA (cpDNA) region, that has been previously proved efficient in discriminating different Quercus taxa, can be employed in distinguishing the Fagus species and in identifying the ancient pollen.

Results

86 populations from 4 Western Euroasistic taxa were sampled, and sequenced for the trn L-trn F region to verify the efficiency of this cpDNA region in identifying the Fagus spp.. Furthermore, Fagus crenata (2 populations), Fagus grandifolia (2 populations), Fagus japonica, Fagus hayatae, Quercus species and Castanea species were analysed to better resolve the phylogenetic inference.Our results show that this cpDNA region harbour some informative sites that allow to infer relationships among the species within the Fagaceae family. In particular, few specific and fixed mutations were able to discriminate and identify all the different Fagus species.Considering a short fragment of 176 base pairs within the trn L intron, 2 transversions were found able in distinguishing the F. orientalis complex taxa (F. orientalis, F. taurica and F. moesiaca) from the remaining Fagus spp. (F. sylvatica, F. japonica, F. hayataea, F. crenata and F. grandifolia). This permits to analyse this fragment also in ancient samples, where DNA is usually highly degraded.The sequences data indicate that the DNA recovered from ancient pollen belongs to the F. orientalis complex since it displays the informative sites characteristic of this complex.

Conclusion

The ancient DNA sequences demonstrate for the first time that, in contrast to current knowledge based on palynological and macrofossil data, the F. orientalis complex was already present during the Tyrrhenian period in what is now the Venice lagoon (Italy).This is a new and important insight considering that nowadays West Europe is not the natural area of Fagus orientalis complex, and up to now nobody has hypothesized the presence during the Last Interglacial period of F. orientalis complex in Italy.