In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

The impact of perfectionism and anxiety traits on action monitoring in major depressive disorder

Perfectionism and anxiety features are involved in the clinical presentation and neurobiology of major depressive disorder (MDD). In MDD, cognitive control mechanisms such as action monitoring can adequately be investigated applying electrophysiological registrations of the error-related negativity (ERN) and error positivity (Pe). It is also known that traits of perfectionism and anxiety influence ERN amplitudes in healthy subjects. The current study explores the impact of perfectionism and anxiety traits on action monitoring in MDD. A total of 39 MDD patients performed a flankers task during an event-related potential (ERP) session and completed the multidimensional perfectionism scale (MPS) with its concern over mistakes (CM) and doubt about actions (DA) subscales and the trait form of the State Trait Anxiety Inventory. Multiple regression analyses with stepwise backward elimination revealed MPS-DA to be a significant predictor (R2:0.22) for the ERN outcomes, and overall MPS (R2:0.13) and MPS-CM scores (R2:0.18) to have significant predictive value for the Pe amplitudes. Anxiety traits did not have a predictive capacity for the ERPs. MPS-DA clearly affected the ERN, and overall MPS and MPS-CM influenced the Pe, whereas no predictive capacity was found for anxiety traits. The manifest impact of perfectionism on patients’ error-related ERPs may contribute to our understanding of the action-monitoring process and the functional significance of the Pe in MDD. The divergent findings for perfectionism and anxiety features also indicate that the wide range of various affective personality styles might exert a different effect on action monitoring in MDD, awaiting further investigation

The Mitotic Arrest Deficient Protein MAD2B Interacts with the Small GTPase RAN throughout the Cell Cycle

Contains fulltext : 81260.pdf (publisher's version ) (Open Access)BACKGROUND: Previously, we identified the mitotic arrest deficient protein MAD2B (MAD2L2) as a bona fide interactor of the renal cell carcinoma (RCC)-associated protein PRCC. In addition, we found that fusion of PRCC with the transcription factor TFE3 in t(X;1)(p11;q21)-positive RCCs results in an impairment of this interaction and, concomitantly, an abrogation of cell cycle progression. Although MAD2B is thought to inhibit the anaphase promoting complex (APC) by binding to CDC20 and/or CDH1(FZR1), its exact role in cell cycle control still remains to be established. METHODOLOGY/PRINCIPAL FINDINGS: Using a yeast two-hybrid interaction trap we identified the small GTPase RAN, a well-known cell cycle regulator, as a novel MAD2B binding protein. Endogenous interaction was established in mammalian cells via co-localization and co-immunoprecipitation of the respective proteins. The interaction domain of RAN could be assigned to a C-terminal moiety of 60 amino acids, whereas MAD2B had to be present in its full-length conformation. The MAD2B-RAN interaction was found to persist throughout the cell cycle. During mitosis, co-localization at the spindle was observed. CONCLUSIONS/SIGNIFICANCE: The small GTPase RAN is a novel MAD2B binding protein. This novel protein-protein interaction may play a role in (i) the control over the spindle checkpoint during mitosis and (ii) the regulation of nucleocytoplasmic trafficking during interphase

Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo

The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs

Focus on the management of thunderclap headache: from nosography to treatment

Thunderclap headache (TCH) is an excruciating headache characterized by a very sudden onset. Recognition and accurate diagnosis of TCH are important in order to rule out the various, serious underlying brain disorders that, in a high percentage of cases, are the real cause of the headache. Primary TCH, which may recur intermittently and generally has a spontaneous, benign evolution, can thus be diagnosed only when all other potential underlying causes have been excluded through accurate diagnostic work up. In this review, we focus on the management of TCH, paying particular attention to the diagnostic work up and treatment of the condition

B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease

Background: The role of B cells in allergic asthma remains undefined. One mechanism by which B cells clearly contribute to allergic disease is via the production of specific immunoglobulin, and especially IgE. Cognate interactions with specific T cells result in T cell help for B cells, resulting in differentiation and immunoglobulin secretion. Proximal to (and required for) T cell-dependent immunoglobulin production, however, is antigen presentation by B cells. While interaction with T cells clearly has implications for B cell function and differentiation, this study investigated the role that B cells have in shaping the T cell response during chronic allergic lung disease. Methodology/Principal Findings: In these studies, we used a clinically relevant mouse model of chronic allergic lung disease to study the role of B cells and B cell antigen presentation in this disease. In these studies we present several novel findings: 1) Lung B cells from chronically allergen challenged mice up-regulated MHC II and costimulatory molecules CD40, CD80 and CD86. 2) Using in vitro studies, B cells from the lungs of allergen challenged mice could present antigen to T cells, as assessed by T cell proliferation and the preferential production of Th2 cytokines. 3) Following chronic allergen challenge, the levels of Th2 cytokines IL-4 and IL-5 in the lungs and airways were significantly attenuated in B cell 2/2 mice, relative to controls. 4) B cell driven Th2 responses and mucus hyper secretion in the lungs were dependent upon MHC II expression by B cells. Conclusions/Significance: Collectively, these results provide evidence for antigen presentation as a novel mechanism b

Sucrose in the concentrated solution or the supercooled “state” : a review of caramelisation reactions and physical behaviour

Sucrose is probably one of the most studied molecules by food scientists, since it plays an important role as an ingredient or preserving agent in many formulations and technological processes. When sucrose is present in a product with a concentration near or greater than the saturation point—i.e. in the supercooled state—it possesses high potentialities for the food industry in areas as different as pastry industry, dairy and frozen desserts or films and coatings production. This paper presents a review on critical issues and research on highly concentrated sucrose solutions—mainly, on sucrose thermal degradation and relaxation behaviour in such solutions. The reviewed works allow identifying several issues with great potential for contributing to significant advances in Food Science and Technology.Authors are grateful for the valuable discussions with Teresa S. Brandao and Rosiane Lopes da Cunha during this research. Author M. A. C. Quintas acknowledges the financial support of her research by FCT grant SFRH/BPD/41715/2007

SS18 Together with Animal-Specific Factors Defines Human BAF-Type SWI/SNF Complexes

Contains fulltext : 94049.pdf (publisher's version ) (Open Access

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta