Strategy to Probe the Local Atomic Structure of Luminescent Rare Earth Complexes by X-ray Absorption Near-Edge Spectroscopy Simulation Using a Machine Learning-Based PyFitIt Approach.

Rare earth(III) ß-diketonates are highly remarkable luminophores in the visible spectral region among the rare earth compounds, owing to the efficient contribution from the 4f-4f intraconfigurational transitions. To get detailed structural insight into the RE3+ sites (RE = Eu, Gd, and Sm), X-ray absorption near-edge spectroscopy (XANES) can be very potent in probing the local chemical environment around the RE3+ ion. In this work, a PyFitIt machine learning approach was employed as a new strategy to simulate the Eu, Gd, and Sm L3-edge XANES and thereby determine the local atomic structure of the luminescence RE3+ ß-diketonate complexes, [Eu(tta)3(H2O)2], [C4mim][Eu(dbm)4], [Gd(tta)3(H2O)2], and [Sm(dbm)3(phen)] (tta, 3-thenoyltrifluoroacetonate; dbm, dibenzoylmethane; phen, phenanthroline; and C4mim, 1-butyl-3-methylimidazolium bromide). Continuous Cauchy wavelet transform validated the PyFitIt calculated XANES by visualizing very efficiently the coordination geometries, composed of O and O/N backscatterers around the RE3+ (RE = Eu and Gd) and Sm3+ ions, respectively, as a pinkish-red color map in the two-dimensional images of the corresponding complexes. Extended X-ray absorption fine structure fit in Artemis also corroborated the three-dimensional structures generated by PyFitIt XANES simulation for all the compounds. Though, relatively slightly higher bond distance values for the Sm3+ complex are due to the higher atomic radius of the Sm3+ ion when compared to the Eu3+ and Gd3+ complexes. Meanwhile, higher Debye-Waller factor (σ2) values for the [C4mim][Eu(dbm)4] when compared to the [Eu(tta)3(H2O)2] indicated the structure disorder, owing to the distortion in the local geometry. It is noteworthy that the optical properties, described mainly by the Ωλ (λ = 2 and 4) 4f-4f intensity parameters, are very sensitive to the local coordination environment around the Eu3+ ion. Thus, a close agreement between the experimental and theoretically calculated Ωλ parameter values confirmed that the PyFitIt calculated square antiprismatic structures are precisely similar to the real structures of the Eu3+ complexes.

Dragonflies and damselflies (Odonata) from Puerto Rico: a checklist with notes on distribution and habitat.

BACKGROUND: Conservation of tropical freshwater fauna requires a solid understanding of species biodiversity patterns. We provide an up to date annotated list of Odonata of Puerto Rico, which is based on current reports. The list is complemented with notes on the geographic and altitudinal distribution of this order on the island. We also compare current composition relative to early reports conducted when Puerto Rico was mostly an agricultural region. METHODS: We surveyed adult Odonata all over Puerto Rico with the aid of undergraduate students. Students were trained on capturing, preserving, and data basing specimens. All material was centralized, identified by the lead author, and deposited in the Zoology Museum at the University of Puerto Rico (MZUPR), Río Piedras campus. Surveys were complemented with focal collections by the authors and a literature review of published records for Puerto Rico and the Caribbean. We requested records from specialists to obtain the most complete list of species for the island. RESULTS: An annotated list of Odonata from Puerto Rico is presented, reporting 49 species distributed in two suborders and four families. We provide information on species distribution among municipalities and elevations around Puerto Rico. A historic list of species was developed for the 1930s-1940s, when agriculture covered most of Puerto Rico, based on literature and museum specimens. Both current and historic records are similar and suggest that the Odonata fauna is dominated by generalist species and has changed little since the agricultural period. Our list provides a point of reference to understand biodiversity patterns in Puerto Rico and the Caribbean and for assessing the effects of land use change on aquatic insect diversity.

Purification of Native Fasciola hepatica Fatty Acid-Binding Protein and Induction of Alternative Activation of Human Macrophages.

This chapter presents the different techniques to purify the native forms of Fasciola hepatica fatty acid-binding protein (Fh12) using size exclusion chromatography and isoelectric focusing (IEF). Also, it presents the procedure to study the immunological effect of the purified protein Fh12 using monocyte-derived macrophages (MDM) obtained from healthy human donors. For this purpose, I present the procedure to isolate and culture peripheral blood mononuclear cells (PBMCs) to generate alternatively activated macrophages (AAMΦ) by in vitro exposure to Fh12.

Possible Role for Toll-Like Receptors in Interaction of Fasciola hepatica Excretory-Secretory Products with Human Monocyte Cell Line.

This chapter presents a proteomic approach to purify and identify native excretory-secretory products (ESPs) in the range of >10-30 kDa proteins capable of interacting with toll-like receptors (TLRs). Here we present a protocol to fractionate the total ESPs using an ultrafiltration system to recover ESP proteins >10-30 kDa. The fraction of the proteins >10-30 kDa is purified by ion exchange chromatography (IEC) using a mono Q-column in a fast protein liquid chromatography system (FPLC) to separate its components based on charge. Finally, a screening system is presented using THP1-Blue CD14 cells to investigate whether TLRs could also be targeted by Fasciola hepatica ESPs and the interaction with TLR4 using HEK293 Blue-TLR4 cells.

Aging effect on vanadium oxide hybrid nanotubes.

Vanadium oxides present a rich magnetic phase diagram depending on the oxidation state of the V ions. In particular the vanadium oxide nanotubes (VO x NTs) present several promising perspectives for different technological applications for which it is essential to know the oxidation state of V ions, as well as to evaluate the stability with the aging time of the tubes. In this work we present a systematic study of the time evolution of the magnetic properties of VO x NTs. For this complete characterization, we used electron spin resonance (ESR) and dc-susceptibility techniques, which were supplemented with TEM microscopy and XANES. We observed that for aging in normal environmental conditions of pressure, temperature and humidity, the V4+ ions oxidize to V5+ . Although the multiwall tubular structure is maintained, this oxidation process produces a marked change in the magnetic properties. We conclude that the aging of the samples affects the V4+ /V5+ relationship in the VO x NTs, which may contribute to explain the significant dispersion of data reported in the bibliography.

Steps towards XAFS beamline automation and remote access.

Although remote access to beamline synchrotron facilities is now a common operation mode at macromolecular crystallography beamlines thanks to substantial efforts in automated processes for sample preparation and handling, experiment planning and analysis, this is still not the case for XAFS beamlines. Here the experience and developments undertaken at LNLS and Diamond in automation are described, in an attempt to tackle the specific challenges posed by the high variability in experimental conditions and configurations that XAFS measurements require.

Síndrome de rendu osler weber en una adolescente en colombia. reporte de un caso de autopsia / Rendu osler weber syndrome in an adolescent in colombia. an autopsy case report

RESUMEN La telangiectasia hemorrágica hereditaria es una enfermedad genética rara, perteneciente al grupo de púrpuras angiopáticas de tipo congénito, caracterizada por lesiones vasculares, encontrando frecuentemente telangiectasias en piel y mucosa del tracto gastrointestinal, fístulas arteriovenosas pulmonares y malformaciones vasculares en sistema nervioso central. Su manifestación clínica más frecuente son las hemorragias del tracto respiratorio superior. Este es el caso de una adolescente de 13 años con hallazgos de hepatopatía crónica, esplenomegalia difusa, pancitopenia, fístulas arteriovenosas pulmonares, deterioro neurológico progresivo secundario a hemorragia subaracnoidea con posterior defunción. Se realizó autopsia médicocientífica que reveló múltiples telangiectasias en mucosas, cirrosis de Osler, malformaciones arteriovenosas en polígono encefálico, hemorragia intraventricular con extensión subaracnoidea y bronconeumonía bibasal con pleuritis secundaria.

ABSTRACT Hereditary hemorrhagic telangiectasia is a rare genetic disease, belonging to the group of congenital angiopathic purpuras. Vascular injuries characterize it, being the most frequent telangiectasia on the skin and the gastrointestinal tract mucosa, pulmonary arteriovenous fistulas and vascular malformations in the central nervous system. The most frequent clinical manifestations are hemorrhages from the upper respiratory tract. It is presented the case of a 13-year-old girl with findings of chronic liver disease, diffuse splenomegaly, pancytopenia, pulmonary arteriovenous fistulas, progressive neurological deterioration secondary to subarachnoid hemorrhage with subsequent death. A medical-scientific autopsy was carried out that revealed multiple telangiectasias in mucous membranes, Osler's cirrhosis, arteriovenous malformations in the brain polygon, intraventricular hemorrhage with subarachnoid extension, and bibasal bronchopneumonia with secondary pleuritis.

Fasciola hepatica ESPs Could Indistinctly Activate or Block Multiple Toll-Like Receptors in a Human Monocyte Cell Line.

Fasciola hepatica is a parasitic helminth that induces Th2/Treg responses in its mammalian host. Some reports have suggested that ESPs achieve these polarized immune responses by delaying the activation of dendritic cells and macrophages during the early stages of innate immunity, a process that is mediated by TLR4. The present study aimed to investigate whether TLRs other than TLR4 could also be targeted by F. hepatica ESPs. To achieve this aim a screening system was optimized using THP1-Blue CD14 cells. ESPs were first separated based on their molecular weight and according their net charge by ion exchange chromatography (IEC). Results demonstrated that F. hepatica ESPs mainly cathepsin, serpin and endopin are capable of activating TLR2, TLR4, TLR8 and likely also TLR5 and TLR6. In contrast, fatty acid binding protein strongly suppressed the stimulation induced by various TLR-ligands. Further studies are needed to understand how these apparent contradictory effects of molecules of the same protein mix complement each other in the context of an active infection resulting in the polarized Th2-immune response that characterize F. hepatica infections.

Electronic structures of cyclometalated palladium complexes in the higher oxidation states.

The electronic and redox properties of a series of cyclometalated Pd complexes with oxidation states of +2, +3 and +4 were examined using a range of currently available spectroscopic and electrochemical techniques. Changes in metal-ligand bond lengths were established by X-ray crystallography and correctly predicted by DFT calculations, from which the frontier orbitals and partial atomic charges can be obtained. X-ray absorption spectroscopy (XAS) revealed interesting XANES features that suggest a synergistic relationship between metal-ligand interactions. The electrochemical study of the Pd(ii) dimer was found to contain two sequential oxidative potentials indicative of a weak metal-metal interaction.

Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.

TLR4, the innate immunity receptor for bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. There is a need to develop molecules that block either activation through TLR4 or the downstream signaling pathways to inhibit the storm of inflammation typically elicited by bacterial LPS, which is a major cause of the high mortality associated with bacterial sepsis. We report in this article that a single i.p. injection of 15 µg fatty acid binding protein from Fasciola hepatica (Fh12) 1 h before exposure to LPS suppressed significantly the expression of serum inflammatory cytokines in a model of septic shock using C57BL/6 mice. Because macrophages are a good source of IL-12p70 and TNF-α, and are critical in driving adaptive immunity, we investigated the effect of Fh12 on the function of mouse bone marrow-derived macrophages (bmMΦs). Although Fh12 alone did not induce cytokine expression, it significantly suppressed the expression of IL-12, TNF-α, IL-6, and IL-1ß cytokines, as well as inducible NO synthase-2 in bmMΦs, and also impaired the phagocytic capacity of bmMΦs. Fh12 had a limited effect on the expression of inflammatory cytokines induced in response to other TLR ligands. One mechanism used by Fh12 to exert its anti-inflammatory effect is binding to the CD14 coreceptor. Moreover, it suppresses phosphorylation of ERK, p38, and JNK. The potent anti-inflammatory properties of Fh12 demonstrated in this study open doors to further studies directed at exploring the potential of this molecule as a new class of drug against septic shock or other inflammatory diseases.

Compact Ag@Fe3O4 core-shell nanoparticles by means of single-step thermal decomposition reaction.

A temperature pause introduced in a simple single-step thermal decomposition of iron, with the presence of silver seeds formed in the same reaction mixture, gives rise to novel compact heterostructures: brick-like Ag@Fe3O4 core-shell nanoparticles. This novel method is relatively easy to implement, and could contribute to overcome the challenge of obtaining a multifunctional heteroparticle in which a noble metal is surrounded by magnetite. Structural analyses of the samples show 4 nm silver nanoparticles wrapped within compact cubic external structures of Fe oxide, with curious rectangular shape. The magnetic properties indicate a near superparamagnetic like behavior with a weak hysteresis at room temperature. The value of the anisotropy involved makes these particles candidates to potential applications in nanomedicine.

Fasciola hepatica fatty acid binding protein induces the alternative activation of human macrophages.

The liver fluke Fasciola hepatica is a highly evolved parasite that uses sophisticated mechanisms to evade the host immune response. The immunosuppressive capabilities of the parasite have been associated with antigens secreted through the parasite's tegument, called excretory-secretory products (ESPs). Proteomic studies have identified the fatty acid binding protein (FABP) as one of molecules present in the parasite ESPs. Although FABP has been investigated for potential use in the development of vaccines against fascioliasis, its direct interaction with cells of immune system has not been studied. In this study, FABP was purified in native form from soluble extracts of F. hepatica adult flukes using a combination of molecular sieving chromatography and preparative isoelectric focusing. The immunological effect of the purified protein, termed Fh12, was assayed in vitro using monocyte-derived macrophages (MDM) obtained from healthy human donors. Results from the assay indicate that Fh12 produced a significantly increased arginase expression and activity and induced the expression of chitinase-3-like protein (CHI3L1). The assay also showed that Fh12 downregulated the production of nitric oxide (NO) and the expression of nitric oxide synthase (NOS2). This indicates that Fh12 induced the production of alternatively activated macrophages (AAMϕ). The results also demonstrated the ability of Fh12 to downregulate the secretion of the proinflammatory and inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-1ßB, even after stimulation with lipopolysaccharide (LPS), as well as its ability to stimulate the overexpression of IL-10. These results suggest a potent anti-inflammatory role for Fh12, which could occur via targeting of Toll-like receptor 4 (TLR4).

A gene signature combining the tissue expression of three angiogenic factors is a prognostic marker in early-stage non-small cell lung cancer.

BACKGROUND: Angiogenesis and lymphangiogenesis are key mechanisms for tumor growth and dissemination. They are mainly regulated by the vascular endothelial growth factor (VEGF) family of ligands and receptors. The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve characterization of patients with worse clinical outcomes. METHODS: RNA was obtained from tumor and normal lung specimens from 175 patients. Quantitative polymerase chain reaction was performed to analyze the relative expression of HIF1A, PlGF, VEGFA, VEGFA165b, VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2. RESULTS: Univariate analysis showed that tumor size and ECOG-PS are prognostic factors for time to progression (TTP) and overall survival (OS). This analysis in the case of angiogenic factors also revealed that PlGF, VEGFA, VEGFB and VEGFD distinguish patients with different outcomes. Taking into account the complex interplay between the different ligands of the VEGF family and to more precisely predict the outcome of the patients, we considered a new analysis combining several VEGF ligands. In order to find independent prognostic variables, we performed a multivariate Cox analysis, which showed that the subgroup of patients with higher relative expression of VEGFA plus lower VEGFB and VEGFD presented the poorest outcome for both TTP and OS. CONCLUSIONS: The relative expression of these three genes can be considered as an angiogenic gene signature whose applicability for the selection of candidates for targeted therapies needs to be further validated.

Fasciola hepatica saposin-like protein-2-based ELISA for the serodiagnosis of chronic human fascioliasis.

An indirect enzyme-linked immunosorbent assay (ELISA) was developed and evaluated for its diagnostic ability to detect human IgG antibodies against Fasciola hepatica saposin-like protein-2. The assay was compared with an indirect ELISA with excretory-secretory products (FhES) from adult F. hepatica. In an analysis of the sera of 37 patients infected with F. hepatica, 40 patients with other parasitic infections, and 50 healthy controls, the sensitivity of both ELISA assays was 100%. However, the FhSAP2-based ELISA was more specific (95.6%) than the FhES-ELISA (91.9%). These results demonstrated that FhSAP2 can be used in the serodiagnosis of chronic human fascioliasis with the additional advantage of being relatively cheap and easy to produce. Studies are in progress to evaluate this FhSAP2-ELISA assay in a large-scale prevalence surveys in endemic areas.