Characterization of the GM1 oligosaccharide transport across the blood-brain-barrier

Ganglioside GM1 has demonstrated to attenuate Parkinson Disease (PD) symptoms in clinical and preclinical trials. Nevertheless, the GM1 efficacy revealed in vitro is critically reduced in vivo, because of the amphiphilic behavior that limits the passage across the blood brain barrier (BBB). In vitro and in vivo experiments showed that GM1 exerts neurotrophic functions by interacting with plasma membrane (PM) proteins throughout its oligosaccharide portion (OligoGM1). Furthermore, OligoGM1 intravenously or subcutaneously injected into mice is absorbed and taken up by different organs and tissues, including brain. In order to take advantage of GM1 oligosaccharide properties and to overcome GM1 pharmacological limitation, this study has been aimed by the investigation of the OligoGM1 transportthrough the BBB, by using a human in vitro model for human brain-like endothelial cells (hBLEC). Ruled out the toxicity of OligoGM1 on hBLEC, the OligoGM1 transport across the hBBB has been analyzed, finding out a 20 fold higher rate than GM1 and a time and concentration dependence. In order to characterize the OligoGM1 passage, a direct evaluation of the OligoGM1 interaction with the ABC-transporters was carried on, leaving out this way for OligoGM1 transport. Moreover, inverse- and 4\ub0C-transport experiments were performed excluding the implication of the active transport for OligoGM1 passage across the hBLEC, leading to consider the passive-paracellular route. Furthermore, after the hBLEC transport, OligoGM1 maintained its stability and capacity to induce neuritogenesis in the mouse neuroblastoma cells line Neuro2a. This preliminary study has improved the knowledge about the GM1 pharmacological potential by proving that OligoGM1 can cross advantageously the BBB, offering a new promising therapeutic strategy

Âge au premier mariage, contraception et mortalité infantile : influence sur l'évolution de la fécondité d'une population berbère du Haut Atlas marocain (vallée d'Anougal)

L’évolution récente de la fécondité et de ses principaux déterminants dans une population berbère traditionnelle du Haut-Atlas occidental marocain a été caractérisée par une série de trois enquêtes rétrospectives complémentaires. Les résultats obtenus montrent un début de transition démographique. La baisse de la fécondité qui a touché toutes les classes d’âges est à mettre en relation avec un accroissement de l’âge au mariage et une régression de la mortalité infantile. La contraception moderne, quant à elle, ne semble pas avoir encore l’effet escompté.The recent fertility trends within a traditional Berber population of the Western High Atlas mountains (Anougal valley) and the main factors responsible for these trends have been studied during three retrospective and complementary inquiries. Results showed that a demographic transition has started within the population. The decrease in fertility observed in all age classes is related to the increase of age at first marriage and the decrease in infant mortality. The modern contraceptive methods don’t seem to be responsible for the observed  transition

Ultrafast electron/energy transfer and intersystem crossing mechanisms in bodipy-porphyrin compounds

Meso-substituted borondipyrromethene (BODIPY)-porphyrin compounds that include free base porphyrin with two different numbers of BODIPY groups (BDP-TTP and 3BDP-TTP) were designed and synthesized to analyze intramolecular energy transfer mechanisms of meso-substituted BODIPY-porphyrin dyads and the effect of the different numbers of BODIPY groups connected to free-base porphyrin on the energy transfer mechanism. Absorption spectra of BODIPY-porphyrin conjugates showed wide absorption features in the visible region, and that is highly valuable to increase light-harvesting efficiency. Fluorescence spectra of the studied compounds proved that BODIPY emission intensity decreased upon the photoexcitation of the BODIPY core, due to the energy transfer from BODIPY unit to porphyrin. In addition, ultrafast pump-probe spectroscopy measurements indicated that the energy transfer of the 3BDP-TTP compound (about 3 ps) is faster than the BDP-TTP compound (about 22 ps). Since the BODIPY core directly binds to the porphyrin unit, rapid energy transfer was seen for both compounds. Thus, the energy transfer rate increased with an increasing number of BODIPY moiety connected to free-base porphyrin

First light of the VLT planet finder SPHERE. I. Detection and characterization of the sub-stellar companion GJ 758 B

GJ758 B is a brown dwarf companion to a nearby (15.76 pc) solar-type, metal-rich (M/H = +0.2 dex) main-sequence star (G9V) that was discovered with Subaru/HiCIAO in 2009. From previous studies, it has drawn attention as being the coldest (~600K) companion ever directly imaged around a neighboring star. We present new high-contrast data obtained during the commissioning of the SPHERE instrument at the VLT. The data was obtained in Y-, J-, H-, and Ks-bands with the dual-band imaging (DBI) mode of IRDIS, providing a broad coverage of the full near-infrared (near-IR) range at higher contrast and better spectral sampling than previously reported. In this new set of high-quality data, we report the re-detection of the companion, as well as the first detection of a new candidate closer-in to the star. We use the new 8 photometric points for an extended comparison of GJ758 B with empirical objects and 4 families of atmospheric models. From comparison to empirical object, we estimate a T8 spectral type, but none of the comparison object can accurately represent the observed near-IR fluxes of GJ758 B. From comparison to atmospheric models, we attribute a Teff = 600K $\pm$ 100K, but we find that no atmospheric model can adequately fit all the fluxes of GJ758 B. The photometry of the new candidate companion is broadly consistent with L-type objects, but a second epoch with improved photometry is necessary to clarify its status. The new astrometry of GJ758 B shows a significant proper motion since the last epoch. We use this result to improve the determination of the orbital characteristics using two fitting approaches, Least-Square Monte Carlo and Markov Chain Monte Carlo. Finally, we analyze the sensitivity of our data to additional closer-in companions and reject the possibility of other massive brown dwarf companions down to 4-5 AU. [abridged]Comment: 20 pages, 15 figures. Accepted for publication in A&

SPHERE: the exoplanet imager for the Very Large Telescope

Observations of circumstellar environments to look for the direct signal of exoplanets and the scattered light from disks has significant instrumental implications. In the past 15 years, major developments in adaptive optics, coronagraphy, optical manufacturing, wavefront sensing and data processing, together with a consistent global system analysis have enabled a new generation of high-contrast imagers and spectrographs on large ground-based telescopes with much better performance. One of the most productive is the Spectro-Polarimetic High contrast imager for Exoplanets REsearch (SPHERE) designed and built for the ESO Very Large Telescope (VLT) in Chile. SPHERE includes an extreme adaptive optics system, a highly stable common path interface, several types of coronagraphs and three science instruments. Two of them, the Integral Field Spectrograph (IFS) and the Infra-Red Dual-band Imager and Spectrograph (IRDIS), are designed to efficiently cover the near-infrared (NIR) range in a single observation for efficient young planet search. The third one, ZIMPOL, is designed for visible (VIR) polarimetric observation to look for the reflected light of exoplanets and the light scattered by debris disks. This suite of three science instruments enables to study circumstellar environments at unprecedented angular resolution both in the visible and the near-infrared. In this work, we present the complete instrument and its on-sky performance after 4 years of operations at the VLT.Comment: Final version accepted for publication in A&

How does Brazil measure up? Comparing rankings through the lenses of nation brand indexes

A considerable amount of literature has been published on nation brand and yet not much regarding measurement. The purpose of this paper is to examine nation brand indexes and explore the unbalanced outcomes of a country’s position in these recognized instruments. Although research has been carried out on nation brand, no single study exists comparing a country in four diverse nation brand indexes, which are the reputable ones by Anholt (2007), Fetscherin (2010), Fombrun (2014) and Anholt and Govers (2014). This paper also reflects on the critical studies perspective of the place branding research domain, discussed by Lucarelli and Berg (2011). After a qualitative approach applied to Brazil, it is believed that these indexes mutually support and complement each other - even though they use different approaches, methodologies, samples, and data. Moreover, each of them has their own strengths and weaknesses in terms of accuracy and rationality. Findings from this paper’s evaluation may guide nation brand managers, governments, and researchers to recognize that indexes should be taken into account when analysing a nation brand and its complex image. Therefore, this paper contributes to existing knowledge on the critical studies perspective of the contemporary theoretical structure of the place branding research domain by providing a comparative study based on real data-based rankings of nation brand indexes

Perceptions of Preparedness for Interprofessional Practice: A Survey of Health Professional Students at Three Universities

Objective: The purpose of this study was to evaluate health professions students’ understanding of their own and others’ roles on interprofessional (IP) teams, assess students’ perceptions of their preparedness to practice in an IP team, and determine differences by type of learning institution and participation in interprofessional education (IPE). Methods: Medical, nursing, and pharmacy students at three Ohio universities with unique IP learning models were surveyed. Descriptive statistics, analysis of variance (ANOVA), chi-square, and two sample t- tests were used to compare measures of knowledge, IPE participation, and preparedness. Results: Of the 981 invited students, 273 completed the survey (27.8% response). Overall, 70.7% of participants felt prepared to work on an IP team. Those who reported participation in IPE were more likely to feel prepared to practice on an IP team compared to those who did not (76.8% [149/194] vs. 55.3% [42/76], p=0.0005). Participation in IPE did not significantly affect knowledge scores (participators 79.6% vs. non-participators 81.0%, p=0.1731). Those who had higher profession-specific knowledge scores were more likely to feel prepared to work with that specific profession. Conclusions: Participation in IPE activities in the representative institutions was high, as was knowledge of professional roles. Both participation in IPE and increased knowledge of roles were associated with increased student-assessed preparedness. Advancement of skills and behaviors including knowledge of roles and other competencies may all be important. Pharmacy in particular should prioritize IPE as a means to elucidate our role on the patient care team.   Type: Original Researc

Modified Delphi procedure-based expert consensus on endpoints for an international disease registry for Metachromatic Leukodystrophy:The European Metachromatic Leukodystrophy initiative (MLDi)

BACKGROUND: Metachromatic Leukodystrophy (MLD) is a rare lysosomal disorder. Patients suffer from relentless neurological deterioration leading to premature death. Recently, new treatment modalities, including gene therapy and enzyme replacement therapy, have been developed. Those advances increase the need for high-quality research infrastructure to adequately compare treatments, execute post-marketing surveillance, and perform health technology assessments (HTA). To facilitate this, a group of MLD experts started the MLD initiative (MLDi) and initiated an academia-led European MLD registry: the MLDi. An expert-based consensus procedure, namely a modified Delphi procedure, was used to determine the data elements required to answer academic, regulatory, and HTA research questions. RESULTS: Three distinct sets of data elements were defined by the 13-member expert panel. The minimal set (n = 13) contained demographics and basic disease characteristics. The core set (n = 55) included functional status scores in terms of motor, manual, speech and eating abilities, and causal and supportive treatment characteristics. Health-related quality of life scores were included that were also deemed necessary for HTA. The optional set (n = 31) contained additional clinical aspects, such as findings at neurological examination, detailed motor function, presence of peripheral neuropathy, gall bladder involvement and micturition. CONCLUSION: Using a modified Delphi procedure with physicians from the main expert centers, consensus was reached on a core set of data that can be collected retrospectively and prospectively. With this consensus-based approach, an important step towards harmonization was made. This unique dataset will support knowledge about the disease and facilitate regulatory requirements related to the launch of new treatments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-022-02189-w

Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies

Measurements of the cross section for exclusive virtual-photoproduction of rho^0 mesons from hydrogen are reported. The data were collected by the HERMES experiment using 27.5 GeV positrons incident on a hydrogen gas target in the HERA storage ring. The invariant mass W of the photon-nucleon system ranges from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with most of the previous data at W > 4 GeV are well described by a model that infers the W-dependence of the cross section from the dependence on the Bjorken scaling variable x of the unpolarized structure function for deep-inelastic scattering. In addition, a model calculation based on Off-Forward Parton Distributions gives a fairly good account of the longitudinal component of the rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class. Revisions: curves added to Fig. 1, several clarifications added to tex