Role of Cerebellar Interpositus Nucleus in the Genesis and Control of Reflex and Conditioned Eyelid Responses

The role of cerebellar circuits in the acquisition of new motor abilities is still a matter of intensive debate. To establish the contribution of posterior interpositus nucleus (PIN) to the performance and/or acquisition of reflex and classically conditioned responses (CRs) of the eyelid, the effects of microstimulation and/or pharmacological inhibition by muscimol of the nucleus were investigated in conscious cats. Microstimulation of the PIN in naive animals evoked ramp-like eyelid responses with a wavy appearance, without producing any noticeable plastic functional change in the cerebellar and brainstem circuits involved. Muscimol microinjections decreased the amplitude of reflex eyeblinks evoked by air puffs, both when presented alone or when paired with a tone as conditioned stimulus (CS). In half-conditioned animals, muscimol injections also decreased the amplitude and damped the typical wavy profile of CRs, whereas microstimulation of the same sites increased both parameters. However, neither muscimol injections nor microstimulation modified the expected percentage of CRs, suggesting a major role of the PIN in the performance of eyelid responses rather than in the learning process. Moreover, the simultaneous presentation of CS and microstimulation in well trained animals evoked CRs similar in amplitude to the added value of those evoked by the two stimuli presented separately. In contrast, muscimol-injected animals developed CRs to paired CS and microstimulation presentations, larger than those evoked by the two stimuli when presented alone. It is concluded that the PIN contributes to the enhancement of both reflex and conditioned eyelid responses and to the damping of resonant properties of neuromuscular elements controlling eyelid kinematics

Nitric oxide modulates interleukin-2-induced proliferation in CTLL-2 cells

The role of the L-arginine–nitric oxide metabolic pathway was explored for interleukin-2-induced proliferation in the cytotoxic T lymphocyte clone CTLL-2. Specific inhibition of nitric oxide synthase significantly diminished, in a concentration-dependent manner, 3H-thymidine uptake of CTLL-2 cells in response to different concentrations of interleukin 2. Withdrawal of L-arginine from culture medium resulted as potent as the higher inhibition obtained when blocking nitric oxide synthase with L-arginine analogues. Furthermore, intermedial concentrations of Larginine and exogenous nitric oxide donors were found for achieving optimal IL2-induced proliferation of CTLL-2. These findings prompted us to suggest that intra- and/or inter-cellular nitric oxide signalling may contribute to the modulation of the IL2 mitogenic effect upon cytotoxic T lymphocytes

Resolving galaxies in time and space: II: Uncertainties in the spectral synthesis of datacubes

In a companion paper we have presented many products derived from the application of the spectral synthesis code STARLIGHT to datacubes from the CALIFA survey, including 2D maps of stellar population properties and 1D averages in the temporal and spatial dimensions. Here we evaluate the uncertainties in these products. Uncertainties due to noise and spectral shape calibration errors and to the synthesis method are investigated by means of a suite of simulations based on 1638 CALIFA spectra for NGC 2916, with perturbations amplitudes gauged in terms of the expected errors. A separate study was conducted to assess uncertainties related to the choice of evolutionary synthesis models. We compare results obtained with the Bruzual & Charlot models, a preliminary update of them, and a combination of spectra derived from the Granada and MILES models. About 100k CALIFA spectra are used in this comparison. Noise and shape-related errors at the level expected for CALIFA propagate to 0.10-0.15 dex uncertainties in stellar masses, mean ages and metallicities. Uncertainties in A_V increase from 0.06 mag in the case of random noise to 0.16 mag for shape errors. Higher order products such as SFHs are more uncertain, but still relatively stable. Due to the large number statistics of datacubes, spatial averaging reduces uncertainties while preserving information on the history and structure of stellar populations. Radial profiles of global properties, as well as SFHs averaged over different regions are much more stable than for individual spaxels. Uncertainties related to the choice of base models are larger than those associated with data and method. Differences in mean age, mass and metallicity are ~ 0.15 to 0.25 dex, and 0.1 mag in A_V. Spectral residuals are ~ 1% on average, but with systematic features of up to 4%. The origin of these features is discussed. (Abridged)Comment: A&A, accepte

Is Subdural Peritoneal Shunt Placement an Effective Tool for the Management of Recurrent/Chronic Subdural Hematoma?

Objectiveæ To describe a surgical techniqueæand to report using a retrospective studyæthe efficacy of peritoneal shunts for the treatment of recurrent/chronic subdural hematoma (CSDH). We describeæthe considerations, complications, and outcomes related to this technique. Methodsæ In a retrospectiveæcohort study, 125 charts with a diagnosis of subacute/chronic subdural hematoma were assigned for evaluation. Of the charts reviewed, 18 charts were found from subjects with a diagnosis of recurrent sub-acute or chronic subdural hematoma. All patients had undergone initial surgical treatment of their condition followed by peritoneal shunt placement to help alleviate intracranial pressure. Factors including the age, size of subdural hematoma, number of previous events, BMI, complications, survival, and clinical course were analyzed. Resultsæ After subdural peritoneal shunt placement all patients had full neurological recovery with no complaints of headaches, lethargy, weakness, confusion or seizures. None of the cases had new subdural hematoma episodes after placement for a minimum of a two-year period (mean 26.1 months) (range 24.3-48.6 months). No postoperative complications were reported. The rates of postoperative hemorrhage, infection, distal catheter revision, and perioperative seizures was found to be zero percent. Shunt drainage was successful in all cases, draining 85% of the blood in the first 48 hours. There was no significant relationship between complications and the use of anticoagulants four weeks after surgery. Conclusions Peritoneal shunts, though rarely used, are a viable option in the treatment of sub-acute/chronic subdural hematomas. When pursuing this treatment, this technique is recommended to mitigate the risks of repeat surgical intervention and lessen perioperative time in high-risk patients

Anti-tumor activity of functionalized biomimetic magnetite nanoparticles produced in the presence of MamC protein of Magnetococcus marinus MC-1

Magnetite Nanoparticles (MNPs) find many applications, including biotechnology, as they can be manipulated by an external magnetic field and functionalized with different molecules. Magnetotactic bacteria bio-mineralize magnetosomes (membrane-enveloped magnetites), which are the ideal magnetic particle. However, scaling-up magnetosome production is still challenging, so bio-mimetics, i.e. in vitro magnetite synthesis mediated by magnetosome-associated proteins is being explored. Our group is working with MamC from Magnetococcus marinus MC-1 that controls the morphology and size of the crystals, producing well faceted Biomimetic Magnetic Nanoparticles (BMNPs) of ~40 nm, which are paramagnetic at room and body temperature while having a large magnetic moment per particle under an external magnetic field. These BMNPs were cytocompatible and biocompatible in vivo. BMNPs were functionalized (isothermal adsorption) with a monoclonal antibody (mAb) recognizing the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic Doxorubicin (DOXO). The functionalized BMNPs present hyperthermia and were stable at physiological pH, while releasing the adsorbed DOXO at acidic pH. mAb functionalization of BMNPs favored their interaction with cells expressing the Met/HGFR and cellular DOXO uptake and toxicity, which was enhanced upon cell exposition to a continuous magnetic field. Real-time cytotoxicity of the BMNPs showed that DOXO-mAb-BMNPs were significantly more toxic than DOXO-BMNPs on Met/HGFR expressing cells, while no differential toxicity was observed on cells not expressing this receptor. When DOXO-BMNPs were injected intravenously in tumor bearing mice and an external magnetic field was applied there, a higher amount of BMNPs accumulated in the tumor and tumor growth was decreased in comparison to mice in which no magnetic field was applied. These BMNPs could thus represent effective nano-carriers for targeted drug delivery and might be combined with hyperthermia to increase efficiency, resulting in a targeted local treatment of tumors with a decrease in the deleterious systemic side effects

Characterization of a bacteriocin produced by a clinical isolate of Shigella flexneri 2

This study was conducted to determine the emergence of antibiotic resistant/producer strains, focusing the efforts in the search for new antimicrobial compounds. A total of 15,131 fecal samples (CI) were analyzed from patients from acute diarrhea (2015-2017 period) and observed that 1,794 were positive for either E. coli, Shigella or Salmonella presence. The ability of 388 Shigella isolates to produce antimicrobial peptides was determined by deferred-antagonism assay. Here, we observed that 9.02% of the Shigella isolates produced an antimicrobial agent able to inhibit the E. coli AB133 strain growth. The CI172 strain was selected as producer for its antimicrobial characterization. This antagonist compound (ShpCI172) was produced during exponential growth phase and displayed a restricted action spectrum. It is also thermo-resistant and has about 3 kDa molecular mass. The ShpCI172 can be classified as a microcin, since CI172 did not display cross immunity with other well-known microcins. This is the first report where the production of a microcin by a Shigella flexneri 2 strains is described. The use of ShpCI172 microcin may contribute to preventing or controlling diarrheal diseases. This finding represents an important contribution in the biotechnology field for its application in the development of new antibiotics and/or food preservatives agents.Fil: Torrez Lamberti, Monica Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Lopez, Fabian Enrique. Universidad Nacional de Chilecito; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Bianchi, A. M.. Hospital del Niño Jesús; ArgentinaFil: Pescaretti, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Delgado, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics

[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.This research was funded by Ministerio de Ciencia e Innovación (AP2007-03456) and the Universidad CEU Cardenal Herrera.Calatayud-Pascual, M.; Sebastian-Morelló, M.; Balaguer-Fernandez, C.; Delgado-Charro, M.; Lopez-Castellano, A.; Merino Sanjuán, V. (2018). Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics. Pharmaceutics. 10(4):1-15. https://doi.org/10.3390/pharmaceutics10040265S11510

Mapping the Asymmetric Thick Disk I. A Search for Triaxiality

A significant asymmetry in the distribution of faint blue stars in the inner Galaxy, Quadrant 1 (l = 20 to 45 degrees) compared to Quadrant 4 was first reported by Larsen & Humphreys (1996). Parker et al (2003, 2004) greatly expanded the survey to determine its spatial extent and shape and the kinematics of the affected stars. This excess in the star counts was subsequently confirmed by Juric et al. (2008) using SDSS data. Possible explanations for the asymmetry include a merger remnant, a triaxial Thick Disk, and a possible interaction with the bar in the Disk. In this paper we describe our program of wide field photometry to map the asymmetry to fainter magnitudes and therefore larger distances. To search for the signature of triaxiality, we extended our survey to higher Galactic longitudes. We find no evidence for an excess of faint blue stars at l > 55 degrees including the faintest magnitude interval. The asymmetry and star count excess in Quadrant 1 is thus not due to a triaxial Thick Disk.Comment: 36 pages, 8 figures. Accepted by Astronomical Journa

Urea‑functionalized amorphous calcium phosphate nanofertilizers: optimizing the synthetic strategy towards environmental sustainability and manufacturing costs

This work has been performed thanks to the funding by Fondazione CARIPLO (Project No. 2016-0648: Romancing the stone: size-controlled HYdroxyaPATItes for sustainable Agriculture – HYPATIA). JMDL acknowledges Spanish Ministry of Science, Innovation and Universities of Spain (MCIU/AEI/FEDER, UE) for funding through the projects NanoVIT (RTI-2018-095794-A-C22) and NanoSmart (RYC-2016-21042). GBRR also acknowledges the Spanish MICIU for her postdoctoral contract within the Juan de la Cierva Program (JdC-2017). Financial support for this work was also provided by the Marie Skłodowska-Curie Standard Fellowships (888972-PSust- MOF, F.J.C.) within the European Union research and innovation framework programme (2014-2020). We thank Prof. Jan Skov Pedersen (Aarhus University, DK) for technical and scientific assistance on SAXS experiments.Nanosized fertilizers are the new frontier of nanotechnology towards a sustainable agriculture. Here, an efficient N-nanofertilizer is obtained by post-synthetic modification (PSM) of nitrate-doped amorphous calcium phosphate (ACP) nanoparticles (NPs) with urea. The unwasteful PSM protocol leads to N-payloads as large as 8.1 w/w%, is well replicated by using inexpensive technical-grade reagents for cost-effective up-scaling and moderately favours urea release slowdown. Using the PSM approach, the N amount is ca. 3 times larger than that obtained in an equivalent one-pot synthesis where urea and nitrate are jointly added during the NPs preparation. In vivo tests on cucumber plants in hydroponic conditions show that N-doped ACP NPs, with half absolute N-content than in conventional urea treatment, promote the formation of an equivalent amount of root and shoot biomass, without nitrogen depletion. The high nitrogen use efficiency (up to 69%) and a cost-effective preparation method support the sustainable real usage of N-doped ACP as a nanofertilizer.Fondazione Cariplo 2016-0648Spanish Ministry of Science, Innovation and Universities of Spain (MCIU/AEI/FEDER, UE) RTI-2018-095794-A-C22 RYC-2016-21042Marie Sklodowska-Curie Standard Fellowships within the European Union research and innovation framework programme (2014-2020) 888972-PSustMOFSpanish MICIU within the Juan de la Cierva Program (JdC-2017