A multiplex analysis of phonological and orthographic networks.

The study of natural language using a network approach has made it possible to characterize novel properties ranging from the level of individual words to phrases or sentences. A natural way to quantitatively evaluate similarities and differences between spoken and written language is by means of a multiplex network defined in terms of a similarity distance between words. Here, we use a multiplex representation of words based on orthographic or phonological similarity to evaluate their structure. We report that from the analysis of topological properties of networks, there are different levels of local and global similarity when comparing written vs. spoken structure across 12 natural languages from 4 language families. In particular, it is found that differences between the phonetic and written layers is markedly higher for French and English, while for the other languages analyzed, this separation is relatively smaller. We conclude that the multiplex approach allows us to explore additional properties of the interaction between spoken and written language.

Chemical Ecology of the host searching behavior in an Egg Parasitoid: are Common Chemical Cues exploited to locate hosts in Taxonomically Distant Plant Species?

Parasitoids are known to exploit volatile cues emitted by plants after herbivore attack to locate their hosts. Feeding and oviposition of a polyphagous herbivore can induce the emission of odor blends that differ among distant plant species, and parasitoids have evolved an incredible ability to discriminate them and locate their hosts relying on olfactive cues. We evaluated the host searching behavior of the egg parasitoid Cosmocomoidea annulicornis (Ogloblin) (Hymenoptera: Mymaridae) in response to odors emitted by two taxonomically distant host plants, citrus and Johnson grass, after infestation by the sharpshooter Tapajosa rubromarginata (Signoret) (Hemiptera: Cicadellidae), vector of Citrus Variegated Chlorosis. Olfactory response of female parasitoids toward plants with no herbivore damage and plants with feeding damage, oviposition damage, and parasitized eggs was tested in a Y-tube olfactometer. In addition, volatiles released by the two host plant species constitutively and under herbivore attack were characterized. Females of C. annulicornis were able to detect and significantly preferred plants with host eggs, irrespectively of plant species. However, wasps were unable to discriminate between plants with healthy eggs and those with eggs previously parasitized by conspecifics. Analysis of plant volatiles induced after sharpshooter attack showed only two common volatiles between the two plant species, indole and ß-caryophyllene. Our results suggest that this parasitoid wasp uses common chemical cues released by many different plants after herbivory at long range and, once on the plant, other more specific chemical cues could trigger the final decision to oviposit.

Health outcomes, utilization, and equity in Chile: an evolution from 1990 to 2015 and the effects of the last health reform.

OBJECTIVE: Chile is an attractive case study because of the deep political changes that it underwent over a short period of time: from a universal health service (60s), through a neoliberal reform (70s) and onto a series of legislative reforms (80s-90s). This article aims to explore and assess the evolution of health outcomes, equity, and utilization in Chile through the last period of these reforms (1990-2015). STUDY DESIGN: Standardized health equity analysis. METHODS: We conducted a standardized economic analysis on health equity and healthcare utilization using the ADePT software (by the World Bank) and using data from the Chilean National Socio-economic Survey. We evaluated trends of health equity and examined concentration curves of health utilization of healthcare services and health outcomes such as children/elder/pregnant nutritional status, self-reported health, and physical limitations. RESULTS: Health outcomes such as nutritional problems in children and pregnant women were concentrated among the poor, while others such as high-relevance health conditions were similar for poorest and richest households. The concentration indexes for health outcomes suggested that income makes the distribution pro-poor. However, the opposite was true for age, in which the probability of health problems among rich individuals increased with age. The concentration curves for utilization of healthcare services showed that dental visits, laboratory exams, specialty visits, and hospitalizations were concentrated on the richest households, while the use of emergency services and preventive medicine were highly concentrated among poor individuals. CONCLUSIONS: Although a positive trend in the increase of healthcare service use among income groups was observed, a significant impact of the latest health reform was not observed.

Eosinophilic esophagitis: an underdiagnosed cause of dysphagia and food impaction to be recognized by otolaryngologists.

Eosinophilic esophagitis (EoE) is a recently recognised pathologic entity whose prevalence has risen significantly since first being described in 1993. Defined as a chronic, local immune-mediated disease with predominant eosinophil infiltration, it is nowadays the leading cause of dysphagia and food bolus impaction in children and young adults. Genetic and environmental risk factors, and especially food antigens, trigger the disease and are in the focus of investigation as avoidance can cure three quarters of patients. The most common antigen involved is milk, followed by egg and gluten. These patients frequently come undiagnosed to the otolaryngologist with complaints of dysphagia and recurrent non-sharp food impactions, although pharyngolaryngeal reflux symptoms and other airway complaints could also be a first sign. Delayed diagnosis and treatment can produce fibrostenosis of the esophagus that greatly impairs patients' quality of life.In-office transnasal esophagoscopy with esophageal biopsy offers a unique opportunity to promptly diagnose and follow-up these patients, without causing the morbidity of repeated sedations and reducing exploration overload in gastroenterology departments. The search for food-antigen triggers, response evaluation to swallowed steroids, or proton pump inhibitors (PPIs) make multiple endoscopies and biopsies necessary every 6 to 8 weeks.There are three first-line interchangeable treatments with the same recommendation: PPIs, dietary allergen elimination and topical swallowed steroids. The choice should be discussed with the patient on an individual basis.The objective of this article is to raise awareness of this condition, update otolaryngologists with the new EoE consensus, and highlight the need for biopsy in patients with dysphagia to rule out EoE.

Influence of Coastal Submarine Groundwater Discharges on Seagrass Communities in a Subtropical Karstic Environment.

The influence of coastal submarine groundwater discharges (SGD) on the distribution and abundance of seagrass meadows was investigated. In 2012, hydrological variability, nutrient variability in sediments and the biotic characteristics of two seagrass beds, one with SGD present and one without, were studied. Findings showed that SGD inputs were related with one dominant seagrass species. To further understand this, a generalized additive model (GAM) was used to explore the relationship between seagrass biomass and environment conditions (water and sediment variables). Salinity range (21-35.5 PSU) was the most influential variable (85%), explaining why H. wrightii was the sole plant species present at the SGD site. At the site without SGD, GAM could not be performed since environmental variables could not explain a total variance of > 60%. This research shows the relevance of monitoring SGD inputs in coastal karstic areas since they significantly affect biotic characteristics of seagrass beds.

Impact of Exposure of Methicillin-Resistant Staphylococcus aureus to Polyhexanide In Vitro and In Vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative decolonization molecules. The absence of reported severe adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as a topical antiseptic. In the present study, we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced susceptibility to polyhexanide by prolonged stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes and with concomitant decreased susceptibility to daptomycin and other cell wall-active antibiotics. However, the in vitro emergence of reduced susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine. During in vivo polyhexanide clinical decolonization treatment, neither reduced polyhexanide susceptibility nor chlorhexidine cross-resistance was observed. Together, these observations suggest that polyhexanide could be used safely for decolonization of carriers of chlorhexidine-resistant S. aureus strains; they also highlight the need for careful use of polyhexanide at low antiseptic concentrations.

Thermal conductivity of Bi2Te3 nanowires: how size affects phonon scattering.

This work provides an in-depth study of how the thermal conductivity of stoichiometric [110] Bi2Te3 nanowires becomes affected when reducing its diameter from an experimental and theoretical point of view. The thermal conductivity was observed to decrease more than 70% (from 1.78 ± 0.46 W K-1 m-1 to 0.52 ± 0.35 W K-1 m-1) when the diameter of the nanowire was reduced one order of magnitude (from 300 nm to 25 nm). The Kinetic-Collective model was used to understand such a reduction, which can be explained by the impact that surface scattering has in acoustic phonons. The smaller the diameter of the nanowires is, the larger the alteration in the mean free path of the low-frequency phonons is. The model agrees well with the experimental data, and the reduction in the thermal conductivity of the nanowires can be explained in terms of an increment of phonon scattering.

Antimicrobial activity of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA) isolates collected in 2013-2014 at the Geneva University Hospitals.

Ceftaroline is a broad-spectrum antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. Ceftaroline susceptibility of an MRSA set archived between 1994 and 2003 in the Geneva University Hospitals detected a high percentage (66 %) of ceftaroline resistance in clonotypes ST228 and ST247 and correlated with mutations in PBP2a. The ceftaroline mechanism of action is based on the inhibition of PBP2a; thus, the identification of PBP2a mutations of recently circulating clonotypes in our institution was investigated. We analyzed ceftaroline susceptibility in MRSA isolates (2013 and 2014) and established that resistant strains correlated with PBP2a mutations and specific clonotypes. Ninety-six MRSA strains were analyzed from independent patients and were isolated from blood cultures (23 %), deep infections (38.5 %), and superficial (skin or wound) infections (38.5 %). This sample showed a ceftaroline minimum inhibitory concentration (MIC) range between 0.25 and 2 µg/ml and disk diameters ranging from 10 to 30 mm, with a majority of strains showing diameters ≥20 mm. Based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 76 % (73/96) of isolates showed susceptibility to ceftaroline. Nevertheless, we still observed 24 % (23/96) of resistant isolates (MIC = 2 µg/ml). All resistant isolates were assigned to clonotype ST228 and carried the N146K mutation in PBP2a. Only two ST228 isolates showed ceftaroline susceptibility. The decreasing percentage of ceftaroline-resistant isolates in our hospital can be explained by the decline of ST228 clonotype circulating in our hospital since 2008. We present evidence that ceftaroline is active against recent MRSA strains from our hospital; however, the presence of PBP2a variants in particular clonotypes may affect ceftaroline efficacy.

Effects of coordination mode of 2-mercaptothiazoline on reactivity of Au(I) compounds with thiols and sulfur-containing proteins.

Gold(I) based drugs are interesting for their potential medical use. The relatively facile ligand substitution in linear gold(I) compounds makes the identification of active species complicated. Ligands such as PR3 and CN- are likely to be carrier ligands due to their strong trans-directing properties and will dictate the nature of substitution reactions. The 2-mercaptothiazoline (mtz) ligand is an N,S-heterocyclic compound which presents an exocyclic thiol sulfur as well as a heterocyclic nitrogen. The coordination of mtz to transition metals can be modulated by the trans ligand and complexes with metal bound through the nitrogen and/or the exocyclic sulfur are known. Therefore, the complexes [NCAu(N-mtz)] (N-coordinated) and [(Ph3P)Au(S-mtz)] (S-coordinated) were investigated to compare the influence of CN- and PR3 as well as the coordination mode of the mtz ligand on reactivity with thiols and sulfur-containing proteins. As a further comparison the compound [(Ph3P)AuCN] was also studied. Human serum albumin, egg white lysozyme and, principally, the C-terminal zinc finger (ZF2) of the nucleocapsid NCp7protein of HIV-1 were studied. Results from zinc finger studies show that the coordination structure can determine the reactivity toward biomolecules. Due to ligand scrambling, the complex [NCAu(N-mtz)] forms very reactive species in solution generating [NCyAux-biomolecule] adducts, where x,y≤3. The observation by mass spectrometry of [(CN)Au]-ZF confirms the ability of Au(I) compounds to form [(Ligand)Au] adducts on zinc fingers, in contrast to Au(III), where all ligands are lost upon reaction with the zinc finger. On the other hand, [(Ph3P)Au(S-mtz)] also generates the [(Ph3P)2Au]+ species due to ligand scrambling, that showed lower reactivity, probably due to steric hindrance. For this complex [(Ph3P)Au-biomolecule] and [Au-biomolecule] adducts are dominant. The results corroborate the hypothesis of modulation through coordination as the reactivity clearly depends on not only the ligand, but also the coordination mode.

C-Jun N-terminal kinases are required for oncolytic adenovirus-mediated autophagy.

Oncolytic adenoviruses, such as Delta-24-RGD (Δ24RGD), are replication-competent viruses that are genetically engineered to induce selective cancer cell lysis. In cancer cells, Δ24RGD induces massive autophagy, which is required for efficient cell lysis and adenoviral spread. Understanding the cellular mechanisms underlying the regulation of autophagy in cells treated with oncolytic adenoviruses may provide new avenues to improve the therapeutic effect. In this work, we showed that cancer cells infected with Δ24RGDundergo autophagy despite the concurrent activation of the AKT/mTOR pathway. Moreover, adenovirus replication induced sustained activation of JNK proteins in vitro. ERK1/2 phosphorylation remained unchanged during adenoviral infection, suggesting specificity of JNK activation. Using genetic ablation and pharmacological inactivation of JNK, we unequivocally demonstrated that cells infected with Δ24RGD required JNK activation. Thus, genetic co-ablation of JNK1 and JNK2 genes or inhibition of JNK kinase function rendered Δ24RGD-treated cells resistant to autophagy. Accordingly, JNK activation induced phosphorylation of Bcl-2 and prevented the formation of Bcl-2/Beclin 1 autophagy suppressor complexes. Using an orthotopic model of human glioma xenograft, we showed that treatment with Δ24RGD induced phosphorylation and nuclear translocation of JNK, as well as phosphorylation of Bcl-2. Collectively, our data identified JNK proteins as an essential mechanistic link between Δ24RGD infection and autophagy in cancer cells. Activation of JNK without inactivation of the AKT/mTOR pathway constitutes a distinct molecular signature of autophagy regulation that differentiates Δ24RGD adenovirus from the mechanism used by other oncolytic viruses to induce autophagy and provides a new rationale for the combination of oncolytic viruses and chemotherapy.

Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells.

BACKGROUND: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment is therefore essential to achieve a stable and long-lasting remission. METHODS: Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative PCR for mRNA expression, western blot for protein expression and quantitative and qualitative promoter methylation methods. RESULTS: Combinations of melatonin and chemotherapeutic drugs (including temozolomide, current treatment for malignant gliomas) have a synergistic toxic effect on BTSCs and A172 malignant glioma cells. This effect is correlated with a downregulation of the expression and function of the ABC transporter ABCG2/BCRP. Melatonin increased the methylation levels of the ABCG2/BCRP promoter and the effects on ABCG2/BCRP expression and function were prevented by preincubation with a DNA methyltransferase inhibitor. CONCLUSION: Our results point out a possible relationship between the downregulation of ABCG2/BCRP function and the synergistic toxic effect of melatonin and chemotherapeutic drugs. Melatonin could be a promising candidate to overcome multidrug resistance in the treatment of glioblastomas, and thus improve the efficiency of current therapies.

Mapping the first electronic resonances of a Cu phthalocyanine STM tunnel junction.

Using a low temperature, ultrahigh vacuum scanning tunneling microscope (STM), dI/dV differential conductance maps were recorded at the tunneling resonance energies for a single Cu phthalocyanine molecule adsorbed on an Au(111) surface. We demonstrated that, contrary to the common assumption, such maps are not representative of the molecular orbital spatial expansion, but rather result from their complex superposition captured by the STM tip apex with a superposition weight which generally does not correspond to the native weight used in the standard Slater determinant basis set. Changes in the molecule conformation on the Au(111) surface further obscure the identification between dI/dV conductance maps and the native molecular orbital electronic probability distribution in space.

Effects of a 10-year conservation programme on the genetic diversity of the Pottoka pony--new clues regarding their origin.

Here, we present the results of a genetic analysis of 463 Pottoka ponies corresponding to four generations, using 17 microsatellite markers. Ten years after the beginning of the Pottoka conservation programme, the values for the genetic diversity of the breed are still high and stable, indicating the success of the programme. We found null alleles in Pottoka for the ASB23, HMS3 and HTG10 microsatellites. Together with information obtained from other pony breeds from the Iberian Peninsula, this finding indicates that these microsatellites should not be used for phylogenetic analyses or parentage tests, at least for these breeds. The high heterozygosity exhibited by this breed in comparison to other ponies, together with its genetic proximity to the centroid of the allele frequencies, suggest that Pottoka allele frequencies are close to those initially exhibited by the ancestors of current European ponies. The results obtained in the current work, together with results from previous studies of ponies and horses from the Iberian Peninsula, corroborate the idea of a unique origin of all ponies from the European Atlantic Area. In contrast, our results do not corroborate the idea that these are derived from a domestication event in the Iberian Peninsula, nor that they have incorporated ancient Iberian horse genes into their genetic pool to a larger extent than other horse breeds.

Permanent genetic resources added to Molecular Ecology Resources Database 1 October 2011-30 November 2011.

This article documents the addition of 139 microsatellite marker loci and 90 pairs of single-nucleotide polymorphism sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Aglaoctenus lagotis, Costus pulverulentus, Costus scaber, Culex pipiens, Dascyllus marginatus, Lupinus nanus Benth, Phloeomyzus passerini, Podarcis muralis, Rhododendron rubropilosum Hayata var. taiwanalpinum and Zoarces viviparus. These loci were cross-tested on the following species: Culex quinquefasciatus, Rhododendron pseudochrysanthum Hay. ssp. morii (Hay.) Yamazaki and R. pseudochrysanthum Hayata. This article also documents the addition of 48 sequencing primer pairs and 90 allele-specific primers for Engraulis encrasicolus.

Genetic variation of toll-like receptor genes and infection by Mycobacterium avium ssp. paratuberculosis in Holstein-Friesian cattle.

Toll-like receptors (TLR) are membrane proteins that play a key role in innate immunity, by recognizing pathogens and subsequently activating appropriate responses. Mutations in TLR genes are associated with susceptibility to inflammatory and infectious diseases in humans. In cattle, 3 members of the TLR family, TLR1, TLR2, and TLR4, are associated with Mycobacterium avium ssp. paratuberculosis infection, although the extent of this association for the TLR1 and TLR4 receptors has not yet been determined. Moreover, the causal variant in the TLR2 gene has not yet been unequivocally established. In this study, 24 single nucleotide polymorphisms (SNP) in the bovine TLR1, TLR2, and TLR4 genes were selected from the literature, databases, and in silico searches, for a population-based genetic association study of a Spanish Holstein-Friesian sample. Whereas previous results regarding the TLR1 gene were not corroborated, a risk haplotype was detected in TLR2; however, its low frequency indicates that this detected association should be interpreted with caution. In the case of the TLR4 gene, 3 tightly linked SNP were found to be associated with susceptibility to M. avium ssp. paratuberculosis infection. Moreover, one of these SNP, the SNP c.-226G>C, which is localized in the 5'UTR region of the TLR4 gene, has been reported to be able to alter TLR4 expression, raising the possibility that this mutation may contribute to the response of the individual to infection.

SP110 as a novel susceptibility gene for Mycobacterium avium subspecies paratuberculosis infection in cattle.

The intracellular pathogen resistance 1 (Ipr1) gene has been reported to play a role in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, and polymorphisms of its human ortholog, SP110 nuclear body protein, have been suggested to be associated with tuberculosis. Thus, the bovine SP110 gene was considered to be a promising candidate for a genetic association study of bovine paratuberculosis, or Johne's disease, a chronic granulomatous enteritis caused by Mycobacterium avium ssp. paratuberculosis (MAP). Initially, single nucleotide polymorphisms (SNP) within the bovine SP110 gene were identified, and subsequently a population-based genetic association study was carried out. Seventeen new SNP along the SP110 gene were identified in Holstein-Friesian cattle, and 6 more were compiled from public databases. A total of 14 SNP were included in the association study of 2 independent populations. The SNP c.587A>G was found to be significantly associated with MAP infection, with the major allele A appearing to confer greater disease susceptibility in one of the analyzed populations. In addition, 2 haplotypes containing this SNP were also found to be associated with infection in the same population. The SNP c.587A>G is a nonsynonymous mutation that causes an amino acid change in codon 196 from asparagine to serine. In silico analyses point to SNP c.587A>G as a putative causal variant for susceptibility to MAP infection. The elucidation of the precise mechanism by which this SNP can exert its effect in the protein and, as a result, in the risk of infection, requires future functional analyses. Likewise, the absence of genetic association in one of the analyzed populations renders it necessary to carry out this study in other independent populations, with the aim of substantiating the repeatability of the present results. Nevertheless, the present results deepen our understanding of the genetic basis of susceptibility and resistance mechanisms related to MAP infection in cattle and, in turn, constitute a step forward toward the implementation of marker-assisted selection in breeding programs aimed at controlling paratuberculosis.

Genetic association between bovine NOD2 polymorphisms and infection by Mycobacterium avium subsp. paratuberculosis in Holstein-Friesian cattle.

Nucleotide-Binding Oligomerization Domain 2 (NOD2) has been reported to be a candidate gene for Mycobacterium avium subsp. paratuberculosis (MAP) infection in a Bos taurus × Bos indicus mixed breed based on a genetic association with the c.2197T>C single nucleotide polymorphism (SNP). Nevertheless, this SNP has also been reported to be monomorphic in the B. taurus species. In the present work, 18 SNPs spanning the bovine NOD2 gene have been analysed in a genetic association study of two independent populations of Holstein-Friesian cattle. We found that the C allele of SNP c.*1908C>T, located in the 3'-UTR region of the gene, is significantly more frequent in infected animals than in healthy ones, which supports the idea that the bovine NOD2 gene plays a role in susceptibility to MAP infection. However, in silico analyses of the NOD2 nucleotide sequence did not yield definitive data about a possible direct effect of SNP c.*1908C>T on susceptibility to infection and led us to consider its linkage disequilibrium with the causative variant. A more exhaustive genetic association study including all putative, functional SNPs from this gene and subsequent functional analyses needs to be conducted to achieve a more complete understanding of how different variants of NOD2 may affect susceptibility to MAP infection in cattle.

Identification of single nucleotide polymorphisms in the bovine solute carrier family 11 member 1 (SLC11A1) gene and their association with infection by Mycobacterium avium subspecies paratuberculosis.

Johne's disease is a chronic enteritis caused by Mycobacterium avium ssp. paratuberculosis (MAP) that causes substantial financial losses for the cattle industry. Susceptibility to MAP infection is reported to be determined in part by genetic factors, so marker-assisted selection could help to obtain bovine populations that are increasingly resistant to MAP infection. Solute carrier family 11 member 1 (SLC11A1) was adjudged to be a potential candidate gene because of its role in innate immunity, its involvement in susceptibility to numerous intracellular infections, and its previous association with bovine MAP infection. The objectives of this study were to carry out an exhaustive process of discovery and compilation of polymorphisms in SLC11A1 gene, and to perform a population-based genetic association study to test its implication in susceptibility to MAP infection in cattle. In all, 57 single nucleotide polymorphisms (SNP) were detected, 25 of which are newly described in Bos taurus. Twenty-four SNP and two 3'-untranslated region polymorphisms, previously analyzed, were selected for a subsequent association study in 558 European Holstein-Friesian animals. The SNP c.1067C>G and c.1157-91A>T and a haplotype formed by these 2 SNP yielded significant association with susceptibility to MAP infection. The c.1067C>G is a nonsynonymous SNP that causes an amino acid change in codon 356 from proline to alanine (P356A) that could alter SLC11A1 protein function. This association study supports the involvement of SLC11A1 gene in susceptibility to MAP infection in cattle. Our results suggest that SNP c.1067C>G may be a potential causal variant, although functional studies are needed to assure this point.