Incorporation of Tb and Gd improves the diagnostic functionality of magnetotactic bacteria

Magnetotactic bacteria are envisaged as potential theranostic agents. Their internal magnetic compass, chemical environment specificity and natural motility enable these microorganisms to behave as nanorobots, as they can be tracked and guided towards specific regions in the body and activated to generate a therapeutic response. Here we provide additional diagnostic functionalities to magnetotactic bacteria Magnetospirillum gryphiswaldense MSR 1 while retaining their intrinsic capabilities. These additional functionalities are achieved by incorporating Tb or Gd in the bacteria by culturing them in Tb Gd supplemented media. The incorporation of Tb provides luminescence properties, enabling potential applications of bacteria as biomarkers. The incorporation of Gd turns bacteria into dual contrast agents for magnetic resonance imaging, since Gd adds T1 contrast to the existing T2 contrast of unmodified bacteria. Given their potential clinical applications, the diagnostic ability of the modified MSR 1 has been successfully tested in vitro in two cell models, confirming their suitability as fluorescent markers Tb MSR 1 and dual contrast agents for MRI Gd MSR

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript

Influence of 1 and 25 Hz,1.5 mT Magnetic Fields on Antitumor Drug Potency in a Human Adenocarcinoma Cell Line

The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1 cch . The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P < 0.01), exhibiting 6.1% of survival at 47.5 mg/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 mg/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P < 0.001). Cisplatin showed a significant reduction in the % of survival (44.2-39.1%, P < 0.05) at 25 Hz and 47.5 mg/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1 cch , with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation

Molecular identification of isolates of the Trichophyton mentagrophytes complex

Background: The Trichophyton mentagrophytes complex is the second most common causal agent of dermatophytosis. It comprises five species-T. mentagrophytes, T. interdigitale, T. erinacei, T quinckeanum, and T. benhamie, as well as nine different genotypes of T. mentagrophytes / T. interdigitale-which are morphologically similar; however, their susceptibility to antifungal agents may differ. For targeted therapy and better prognosis, it is important to identify these species at a molecular level. However, since many hospitals lack molecular methods, the actual aetiology of dermatophytosis caused by this complex remains unknown. Objective: To characterize 55 anthropophilic isolates of the T. mentagrophytes complex recovered from a dermatological centre in Yucatan, Mexico. Material and methods: Fifty-five isolates of the T. mentagrophytes complex were obtained from patients with tinea capitis, tinea pedis, tinea corporis, tinea barbae, and tinea unguium. They were characterized by their colonial and microscopic morphology on Sabouraud dextrose agar (SDA) and through the sequencing of a fragment from the region ITS1-5.8S-ITS2. Results: All colonies grown on SDA were white. Forty-six isolates formed colonies with a powdery texture, while nine isolates formed colonies with a velvety texture. The micromorphological features were typical of the T. mentagrophytes complex. The molecular analysis revealed that 55 isolates were microorganisms that belonged to the T. mentagrophytes complex, that 46 formed powdery colonies representing T. mentagrophytes, and that the other nine isolates that formed velvety colonies represented T. interdigitale. The latter nine isolates were obtained from patients with tinea pedis, tinea corporis, and tinea unguium. Conclusions: The colony morphology on SDA led to the identification of 46 isolates as T. mentagrophytes and nine isolates as T. interdigitale. At a molecular level, the species identified by their morphology were identified only as T. mentagrophytes complex

Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin

OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps

ZNF577 Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet

The methylation levels of ZNF577 in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of ZNF577 depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of ZNF577 of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [n = 90; n = 64 (71.1%) overweight/obesity and n = 26 (28.9%) normal-weight] and paired tumor tissue biopsies (n = 8 breast cancer patients with obesity; n = 3/5 premenopausal/postmenopausal women). Differences in methylation levels were evaluated at each CpGs individually and at the mean of the two evaluated CpGs. Adherence to the Mediterranean diet was evaluated using the MEDAS-validated questionnaire, and the consumption of food groups of interest was also evaluated using the recommended intakes of the Sociedad Espanola de Nutricion Comunitaria. The methylation levels of ZNF577 were correlated between paired leukocytes and breast tumor biopsies (r = 0.62; p = 0.001). Moreover, higher methylation was found in leukocytes from patients with obesity (p = 0.002) and postmenopausal patients (p = 0.022) than patients with normal-weight or premenopausal, respectively. After adjusting for the body mass index and age, higher levels of ZNF577 methylation were also found in women with greater adherence to the Mediterranean diet (p = 0.017) or specific foods. Relevantly, the methylation levels of ZNF577 showed a good ability for fish consumption detection [area under the ROC curve (AUC) = 0.72; p = 0.016]. In conclusion, the association between methylation of ZNF577 and adiposity, menopausal state, and adherence to the Mediterranean diet can be detected in the blood leukocytes. The results guarantee the need of performing further studies in longer longitudinal cohorts in order to elucidate the role of ZNF577 methylation in the association between breast cancer, adiposity and dietary patterns

The subpopulation pattern of eel sperm is affected by post-activation time, hormonal treatment and thermal regime

[EN] There has been a marked reduction in natural stocks of eels (genus Anguilla) over the past 60 years, and the culture of eels is still based on the capture of very large quantities of juveniles. It is necessary to close the life cycle in captivity in order to ease the pressure on wild populations. The aims of the present study were to evaluate sperm subpopulations (through cluster analysis of computer-aided sperm analysis data) in the European eel (Anguilla anguilla) and to assess the effects of motility acquisition time after activation (i.e. at 30, 60 and 90 s), the thermal regimen (i.e. 10 degrees C (T10) or 15 degrees C (T15) and up to 20 degrees C, or constant at 20 degrees C (T20)) and hormonal treatments (i.e. human chorionic gonadotropin (hCG), recombinant (r) hCG or pregnant mare serum gonadotropin (PMSG)) on these subpopulations. In all cases, we obtained three subpopulations of spermatozoa: low velocity and linear (S1); high velocity with low linearity (S2); and high velocity and linear (S3; considered high quality). Total motility and S1 were affected by acquisition time; thus, 30 s is recommended as the standard time for motility acquisition. When eels were kept at 20 degrees C (T20), motility data fitted quadratic models, with the highest motility and proportion of S3 between Weeks 8 and 12 after the first injection. Lower temperatures (T10, T15) delayed spermiation and the obtaining of high-quality spermatozoa (S3), but did not seem to alter the spermiation process (similar subpopulation pattern). Conversely, the hormonal treatments altered both the dynamics of the subpopulation pattern and the onset of spermiation (with PMSG delaying it). Total motility and the yield of S3 with the widely used hCG treatment varied throughout the spermiation period. However, using rhCG allowed us to obtain high-quality and constant motility for most of the study (Weeks 7-20), and the S3 yield was also higher overall (61.8 +/- 1.3%; mean +/- s.e.m.) and more stable over time than the other hormonal treatments (averaging 53.0 +/- 1.4%). Using T20 and rhCG would be more economical and practical, allowing us to obtain a higher number of S3 spermatozoa over an extended time.This study was funded by the European Community's 7th Framework Program under the Theme 2 'Food, Agriculture and Fisheries, and Bio-technology', grant agreement no. 245257 (PRO-EEL) and Generalitat Valenciana (ACOMP/2012/086). VG and MCV have predoctoral grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-16009) and Universitat Politecnica de Valencia (UPV) PAID Program (2011-S2-02-6521), respectively. DSP was supported by a contract cofinanced by Ministry of Science and Innovation (MICINN) and UPV (PTA2011-4948-I). FM-P was supported by the Ramon y Cajal program (MICINN, RYC-2008-02560).Gallego Albiach, V.; Vilchez Olivencia, MC.; Peñaranda, D.; Pérez Igualada, LM.; Herraez, MP.; Asturiano Nemesio, JF.; Martinez-Pastor, F. (2015). The subpopulation pattern of eel sperm is affected by post-activation time, hormonal treatment and thermal regime. Reproduction, Fertility and Development. 27(3):529-543. https://doi.org/10.1071/RD13198S52954327

Distributionally chaotic families of operators on Fréchet spaces

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Communications on Pure and Applied Analysis (CPAA) following peer review. The definitive publisher-authenticated version Conejero, J. A., Kostić, M., Miana, P. J., & Murillo-Arcila, M. (2016). Distributionally chaotic families of operators on Fréchet spaces.Communications on Pure and Applied Analysis, 2016, vol. 15, no 5, p. 1915-1939, is available online at: http://dx.doi.org/10.3934/cpaa.2016022The existence of distributional chaos and distributional irregular vectors has been recently considered in the study of linear dynamics of operators and C-0-semigroups. In this paper we extend some previous results on both notions to sequences of operators, C-0-semigroups, C-regularized semigroups, and alpha-timesintegrated semigroups on Frechet spaces. We also add a study of rescaled distributionally chaotic C-0-semigroups. Some examples are provided to illustrate all these results.The first and fourth authors are supported in part by MEC Project MTM2010-14909, MTM2013-47093-P, and Programa de Investigacion y Desarrollo de la UPV, Ref. SP20120700. The second author is partially supported by grant 174024 of Ministry of Science and Technological Development, Republic of Serbia. The third author has been partially supported by Project MTM2013-42105-P, DGI-FEDER, of the MCYTS; Project E-64, D.G. Aragon, and Project UZCUD2014-CIE-09, Universidad de Zaragoza. The fourth author is supported by a grant of the FPU Program of Ministry of education of Spain.Conejero, JA.; Kostic, M.; Miana Sanz, PJ.; Murillo Arcila, M. (2016). Distributionally chaotic families of operators on Fréchet spaces. Communications on Pure and Applied Analysis. 15(5):1915-1939. https://doi.org/10.3934/cpaa.2016022S1915193915

Better the Devil that You Know: Evidence on Entry Costs Faced by Foreign Banks

Institutional and legal differences between countries increase entry costs and reduce the ability of banks to expand abroad. We use bilateral foreign banking data for 176 countries to estimate a gravity model in which bilateral cross-border banking activity is explained, in addition to standard variables, by legal and institutional differences. We find that foreign banking is negatively affected by absolute differences in the legal setup and in basic institutions between source and host countries. Differences in the legal origin, for example, reduce bilateral participation in the banking system by nearly 11 percent. Additionally we do not find strong evidence suggesting asymmetries in adapting to better or worse institutional/legal environments

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

INTRODUCTION: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. METHODS: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. RESULTS: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. DISCUSSION: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series